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Clinical trial
Last Verified: March/31/2020
First Submitted: April/9/2020
First Posted: April/15/2020
Last Update Posted: April/15/2020
Sponsors: Medical University of Graz
Status: Recruiting
Description

In this prospective observational study the course of 30-50 intensive care patients of the University Hospital of Graz is analysed.

It is not possible to give an exact number of cases, because it is not possible to estimate exactly how many COVID-19 patients will be admitted to the listed intensive care units in Graz. Recruitment will start when approved from the ethical board and end in June, 2020.

Inclusion criteria

- Admission on an isolation unit - intensive care unit of the University Clinic of Graz

- Detection of a SARS - CoV-2 infection by PCR (tracheal or pharyngeal secretion) or CT examination (with consecutive PCR confirmation)

- male and female sex

- subordinated declaration of consent if possible*

- respiratory insufficiency with indication for non-invasive or invasive ventilation during admission to an intensive care unit

Informed consent

Since the study patients are intensive care patients, it may happen that the informed consent cannot be obtained at the time of admission to the intensive care unit (e.g.: patient is not able to give consent due to mechanical ventilation), in this case the informed consent will be obtained at a later time (e.g.: at the latest upon discharge from the intensive care unit/hospital.

(* In exceptional cases it may happen that patients cannot sign a declaration of consent at admission as well as at discharge from the intensive care unit (e.g.: during the stay continuous mechanical ventilation and death at the intensive care unit).

Study related measures

In addition to the standardized routine laboratory (daily, in the morning approx. 05.00 o'clock), a lipid profile (LDL cholesterol, triglycerides, Lpa, HDL cholesterol, total cholesterol) is taken once upon admission to the intensive care unit in order to determine the cardiovascular risk upon admission to the intensive care unit. This lipid profile is taken with the aid of a vacuette (9 ml corresponds to approx. 2 teaspoons of whole blood).

Study related patient questionnaire for the determination of cardiovascular risk

The patient questionnaire should be filled out by interviewing the patients at the time of admission to the intensive care unit. If the condition of the patients does not allow this, the information in the questionnaire should be carried out by a member of the study staff by researching the patient's medical history (e.g. doctor's letters, electronic data acquisition, etc.). The questionnaire is used to assess the cardiovascular risk (contains medication, past medical history).

Non-study-related measures (standardised routine analyses in an intensive care unit)

To determine the cardiovascular risk:

See Patient Questionnaire, Lipid Status, HbA1c

For follow-up (daily routine laboratory checks):

Blood count, coagulation, liver and kidney counts, triglycerides, biomarkers (CK, CK-MB, TropT, NTproBNP, CRP, PCT, IL-6, D-dimer, LDH, myoglobin).

Other parameters and therapies that are considered in the evaluation or that are used to create the data set:

Fluid introduction, fluid discharge, balance, prone positioning, non-invasive ventilation (PEEP, fiO2), invasive ventilation (ventilation mode, PEEP, Pinsp, fiO2, AF), respiration (respiratory rate, fiO2, SpO2, paO2, pCO2, etCO2), circulation parameters (RR syst, RR dia, MAP, HF, ECG (rhythm, Qtc)), extracorporeal organ support procedures, mortality, med. complications, entire drug therapy (e.g: norepinephrine (incl. dose), levosimendan (incl. dose), vasopressin (incl. dose), cortisone (incl. dose), dobutamine (incl. dose), supportive therapy (zinc, vitamin C, selenium), antifungal and antibiotic therapy, hydroxychloroquine, lopinavir, remdesivir, favipiravir, tocilizumab.

Anonymisation of patients

After enrolment in the study, the patient data is encoded/pseudo-anonymised, i.e. patients are identified with a consecutive ID number (neither name, initials nor laboratory requirement number are recorded). To find out the previous illnesses of intensive care patients it is necessary to create a list of patient names and the corresponding ID numbers for pseudonymisation. This list remains with the investigator.

Use of clinical data For the statistical analysis, clinical data in pseudo-anonymised/encoded form are used, e.g. diagnosis, concomitant diseases, long-term medication, intensive care therapy, medication, smoking, age, sex.

Should further questions arise during the study regarding this patient collective, the collected data would be used for further evaluations.

Centre/intensive care units The test centre is the LKH Univ.Klinikum Graz, Auenbruggerplatz 5, A-8036 Graz. Patients are admitted to the SARS - CoV-2 (COVID-19) isolation unit intensive care units of the LKH University Hospital Graz.

Condition or disease
Condition or disease: Risk Factor, Cardiovascular; Covid19; Critical Illness; Course Illness
Location
Austria
Phase
-
Study design
Study type:Observational [Patient Registry]
Observational Model:Cohort
Time Perspective:Prospective
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: April/8/2020
First Posted: April/12/2020
Last Update Posted: April/12/2020
Sponsors: United States Department of Defense
Status: Not yet recruiting
Description

Since December of 2019 COVID-19 is a rapidly spreading virus presently infecting over 1,000,000 individuals worldwide, over 250,000, and over 6,000 deaths in the United States as of 03/31/2020.1

Presently there are no FDA approved treatments or immunizations against COVID-19; however, the FDA has granted an EUA for the treatment of hospitalized patients with hydroxycholorquine.2

Depending on case series the expected case fatality rate for COVID-19 without treatment is between 0.5-10% with the most likely range between 1-3% which is>>10x the expected case fatality rate of seasonal influenza.

Several studies have reported anecdotal and promising preliminary data on the treatment of Coronavirus. Based on the limited evidence from these studies, pre-exposure prophylaxis, or post-exposure prophylaxis may be beneficial.3-21

Due to the nature of the work in the Pentagon multiple critical individuals are unable to practice effective social distancing measures in order to ensure their mission critical jobs for continuity of government and national defense.

Any medication, treatment protocol, or epidemiological control measure which appears safe preliminarily and can be implemented must be tested and put into practice immediately in order to protect senior leaders and other mission critical personnel.

1. https://www.worldometers.info/coronavirus/country/us/

2. EUA Hydroxychloroquine sulfate Health Care Provider Fact Sheet, version date 3/28/2020 - attached in study documents.

3. Colson P, et al. Chloroquine and hydroxychloroquine as available weapons to fightCOVID-19. International Journal of Antimicrobial Agents https://doi.org/10.1016/j.ijantimicag.2020.105932

4. Zhou D, et al. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression, Journal of Antimicrobial Chemotherapy, https://doi.org/10.1093/jac/dkaa114

5. Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia Chinese Journal of Tuberculosis and Respiratory Diseases 43, no. 0. https://www.ncbi.nlm.nih.gov/pubmed/32075365.

6. Yao X, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. https://www.ncbi.nlm.nih.gov/pubmed/32150618.

7. Cortegiana, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Mar 10. https://www.sciencedirect.com/science/article/pii/S0883944120303907.

8. Hydroxychloroquine clinical trial (NCT04261517). https://clinicaltrials.gov/ct2/show/NCT04261517?cond=covid-19&draw=8.

9. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. Accessed 2020 Mar 12. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory- infection-when-novel-coronavirus(ncov)-infection-is-suspected.

10. CDC. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). Accessed 2020 Mar 12. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html .

11. Gross AE, Bryson ML. Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections: A Systematic Review. Ann Pharmacother. 2015 Oct;49(10):1125-35. https://www.ncbi.nlm.nih.gov/pubmed/26228937.

12. Arabi YM, et al. Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study. Clin Infect Dis. 2019 Jun 25. https://www.ncbi.nlm.nih.gov/pubmed/31925415.

13. Mo Y, Fisher D. A review of treatment modalities for Middle East Respiratory Syndrome. J Antimicrob Chemother. 2016 Dec;71(12):33403350. https://www.ncbi.nlm.nih.gov/pubmed/27585965.

14. Darunavir/cobicistat clinical trial (NCT04252274). https://clinicaltrials.gov/ct2/show/NCT04252274.

15. Wang M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research. 2020 30;269-71. https://www.nature.com/articles/s41422-020-0282-0.

16. Gamino-Arroyo AE, et al. Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness. Clin Infect Dis. 2019 Dec 69;11:1903-11. https://academic.oup.com/cid/article/69/11/1903/5308603.

17. Yao TT, et al. A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus-A Possible Reference for Coronavirus Disease-19 Treatment Option. J Med Virol. 2020 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/32104907.

18. Young BE, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Mar 3. https://jamanetwork.com/journals/jama/fullarticle/2762688

19. Li Y, et al. Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response. Microbes Infect. 2013 Feb;15(2):88-95. https://www.ncbi.nlm.nih.gov/pubmed/23123977

20. Xiaoling X, et al. Effective treatment of Severe COVID-19 Patients with Tocilizumab. [Pre-print - not peer reviewed]. http://chinaxiv.org/abs/202003.00026.

21. NephJC (nephrology online journal club) detailed review with links to society statements. Accessed 2020 Mar 16. http://www.nephjc.com/news/covidace2.

The primary aim of this study is to determine whether pre-exposure prophylaxis decreases the incidence of COVID-19 infections amongst personnel, and the secondary aim is to determine whether post-exposure prophylaxis decreases the severity of illness and speeds the return to work of personnel.

The Pentagon Medical Facilities consist of 2 separate medical clinics and 2 separate dental clinics that collaborate on daily activities. Operational personnel with special medical requirements such as aviators and Personnel Reliability Program (PRP) personnel are typically seen in the Pentagon Flight Medicine Clinic while other personnel are seen in the DiLorenzo Tricare Health Clinic Pentagon.

Based on the EUAs for hydroxychloroquine & chloroquine, which are in critical national shortage, and inpatient treatment protocols, hydroxychloroquine and chloroquine show potential for treatment of patients hospitalized for COVID-19. We suspect that treatment of early or asymptomatic exposed patients with chloroquine may decrease infection rates or limit infection severity if pre-treated or treated early

Describe all the data variables, information to be collected, the source of the data, and how the data will be operationally measured.

Study Procedures:

Inclusion criteria:

All mission critical personnel enrolled to the DiLorenzo Tricare Health Clinic or Pentagon Flight Medicine Clinic unable to telework or appropriately socially distance with access to the Pentagon during the declared public health crisis.

Exclusion criteria:

Known recovered COVID-19 patient, G6PD deficient individuals, individuals with significant QT abnormalities, non-compliant patients, and patients who refuse randomization or consent.

Recruitment by Arms:

1. 2, 3. Individuals will be approached by protocol staff and any other staff added to the protocol after initial submission during their screening for clinical visits or access screening to critical spaces. They will be asked 2 questions:

a. Are you aware of an ongoing study within the Pentagon attempting to determine the efficacy of a medication to prevent or treat COVID-19 infections?

i. If the individual answers yes:

a. Have you already elected or are you interested in participating?

i. If yes they are or are interested in participating they will be referred for enrollment as appropriate.

ii. If not they will be thanked for their time.

ii. If the individual answers no:

a. Would you like to learn more or are you interested in enrolling?

i. Yes: Referred for enrollment.

ii. No: They will be thanked for their time.

4. PIs and AIs who are seeing patients for possible COVID-19 exposure or who have tested positive as part of their routine clinical duties will offer enrollment to arm 4 these individuals. At their first visit.

Consent:

Informed and appropriately witnessed consent* as required will be obtained by the PI or any other AI added in subsequent modifications to the protocol. Due to telemedicine and social distancing with the ongoing crisis this will be by distance mechanisms including digital versus wet signature as clinically indicated based on the situation to minimize patient and provider risks.

Patients will be assigned sequential patient identifier numbers during their consent process for tracking purposes.

Initial procedures for safety monitoring including CBC, CMP, UA, G6PD testing (if prior records unavailable), and EKG (if prior records unavailable) will be obtained after consent.

Assignment to groups 1, 2, or 3:

Patients will be randomized to groups 1-3 by a random number generators' results (https://www.google.com/search?sxsrf=ALeKk03SHGo_yHevMbw4jIPVd85kc7e8Sg%3A1586372945822&sourc e=hp&ei=USGOXqqgL6mGytMPo-268Ag&q=random+number+1-3&oq=random+nu&gs_lcp=CgZwc3ktYWIQAxgEMgUIA BCDATICCAAyAggAMgIIADICCAAyAggAMgIIADICCAAyAggAMgIIADoECCMQJzoFCAAQkQJKJAgXEiAwZzE3NGcxNjlnMT czZzc4ZzEwNmc5N2c5OGc4N2c4NUoXCBgSEzBnMWcxZzJnMWcxZzFnMWcxZzFQvQJYhxRg4zdoAXAAeACAAaEBiAH3B5I BAzcuM5gBAKABAaoBB2d3cy13aXo&sclient=psy-ab) pre-recorded in a sealed plain envelope.

Medication retrieval:

The patient will then present to the DTHC pharmacy with their envelope and copy of their enrollment consent to retrieve their medications. The pharmacist will open their envelope and hand them medication 1, 2, or 3 as appropriate, and record their study number and group number on a running spreadsheet maintained without PII in the pharmacy.

Patients will provide their study number to the pharmacy for any refills during the duration of the study.

If an individual is on pre-exposure prophylaxis and develops COVID-19 they will continue on treatment through the post-exposure prophylaxis window of 7 days on the dose they were assigned at randomization.

Records collection:

Patient records will be queried in five ways: 1. At study enrollment 2. During consent patient's will be asked to inform study personnel if they become sick or exposed to COVID-19; patients will present with concerns 3. Monthly records reviews will be conducted to determine if patients have become positive or are displaying signs of COVID-19 4. When the study personnel are informed by public health officials of a positive COVID-19 patient assigned to the Pentagon 5. When the declared public health emergency is over or the study ends (at its 1 year anniversary if the public health emergency has not ended).

Results will be retrieved from AHTLA, CHCS, request to treating civilian providers for care outside the MHS, Essentris, and MHS imaging systems such as Impax.

Records collection will include as appropriate:

1. Date of exposure - to determine optimal timing of post-exposure prophylaxis during data analysis.

2. Date of positive test - to determine optimal timing of post-exposure prophylaxis on data analysis.

3. Medical comorbidities as they are known or become known including HTN, DM, Male Gender, Age, Pulmonary Disease, Health Care Worker / First Responder, and/or known cardiac disease. - to control and test for cofounding conditions as well as risk stratify

4. CXR results, Chest CT results, Intracranial Imaging results, cardiac testing, CBCs, CMPs, COVID-19 test results, Infectious Disease notes, Pulmonary notes, Cardiology/Cardiac surgery notes, and Neurology notes. - to control and test for cofounding conditions as well as risk stratify. To determine whether an individual is safe to enroll and receive study medications. To determine if an individual under therapy has become infected and guage severity of the infection. All imaging being performed is for standard of care and not study purposes.

5. Date of symptom onset - to determine optimal timing of post-exposure prophylaxis during data analysis. To determine time to event.

6. Date of resolution - to assess effects of medication treatment on duration and severity of disease.

7. All medications that the patient is on or has been on within the proceeding 1 month - to assess for possible complications or medication interactions.

8. Hospitiization records, particulary records with regards to ICU admission, ICU discharge, need for supplemental oxygen, length of stay, ICU length of stay, and/or need for mechanical ventilation - to properly assess severity, disease duration, and course for secondary outcome analysis.

9. Date of treatment start - to assess for optimal timing of initiation of secondary prophylaxis or time to onset of symptoms after prophylaxis.

10. Date of treatment termination - to assess for relapses or worsening timing after cessation of treatment.

- Witness:

"In order to conduct human research in this Commonwealth of Virginia, informed consent must be obtained if the person who is to be the human subject is as follows:(i) capable of making an informed decision, then it shall be subscribed to in writing by the person and witnessed; or (ii) incapable of making an informed decision at the time consent is required, then it shall be subscribed to in writing by the person and witnessed. Therefore the "impartial witness" section in the consent form will be used for all subjects consented in the Commonwealth of Virginia.

Responsibilities of the impartial witness include the following:

- Read the informed consent and all written materials given to the subject

- Confirm the subject was presented sufficient information to assure that the subject was truly informed

- Sign and date the informed consent form after the informed consent and any other written information provided to the subject is read and explained.

A signature from the impartial witness will serve as documentation of this process within the subject's study file. The subject will also need to sign and date or mark the informed consent showing appropriate consent for participation."

Condition or disease
Condition or disease: COVID-19
Location
United States
Phase
Phase 2
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: April/6/2020
First Posted: April/8/2020
Last Update Posted: April/13/2020
Sponsors: Tabula Rasa HealthCare
Status: Active, not recruiting
Description

Certain investigational agents have been described in observational series or are being used anecdotally based on in vitro or extrapolated evidence. It is important to acknowledge that there are no controlled data supporting the use of any of these agents, and their efficacy for COVID-19 is unknown. FDA-approved drugs such as chloroquine/hydroxychloroquine, lopinavir/ritonavir, monoclonal IL-6 antibodies, JAK inhibitors, thalidomide and the new investigational drug, remdesivir have been proposed for repurposing to fight COVID-19 and its complications.

A medication risk stratification strategy will be used to simulate the impacts of different potential repurposed drugs for COVID-19 on the Medication Risk Score (MRS) which is used as a predictive tool for ADEs. A retrospective study will be conducted using de-identified drug claims data of elderly patients with polypharmacy.

Patients meeting all the following criteria will be included:

1. Patient enrolled in a PACE organization during the implementation period;

2. PACE organization contractually receiving pharmacy services from CareKinesis;

Exclusion Criteria

a) No drug claims data available for the period of 2019-2020

This retrospective cohort will utilize 178,867 drug claims from approximately 12,123 patients enrolled in PACE. MRS will be calculated using the last available 3-month period of drug claims in 2019. The data elements required for the calculation of the full set of risk scores are: prescribed drugs, dose, age, gender. Medication risk stratification using 5 factors will be performed to obtain the MRS. Various repurposed drugs (drugs associated with the highest probability or efficacy or shown interest as per their inclusion in current clinical trials will be prioritized) will be added to the patient drug regimen except for the patients that are currently taking the repurposed drug. A new MRS will be generated for all stratified patients.

Condition or disease
Condition or disease: COVID; Drug Effect; Drug Interaction; Adverse Drug Event
Location
United States
Phase
-
Study design
Study type:Observational
Observational Model:Cohort
Time Perspective:Retrospective
Eligibility Criteria
Ages Eligible for Study:55 Years to 55 Years
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: April/6/2020
First Posted: April/12/2020
Last Update Posted: April/12/2020
Sponsors: Genesis Foundation
Status: Recruiting
Description

Test plan overview Project phase Phase II

Indication:

Complementary treatment of COVID 19

The purpose of the study:

Examine the efficacy and tolerance of a chlorine dioxide based preparation

Study design:

Quasi-experimental clinical case study

Number of patients expected:

20 patients.

Main inclusion criteria:

COVID 19 infection

Substance or study drug:

Chlorine dioxide 3,000 ppm administered in dilutions in water.

Dosage:

10 cc of Chlorine Dioxide 3,000 ppm diluted in one liter of water to take in equal doses in 24 hours.

Route and duration of administration of the medication. The medication will be taken orally for one month.

Main efficacy criteria:

Assessment according to "visual analog scale" (VAS), 10-point scale (1 = poor VAS; 10 = optimal) evaluation by patients.

Negativization of COVID 19 in the patient.

Tolerance criteria:

Adverse reactions Semiological, clinical and laboratory explorations are expected at the beginning of the study treatment (or baseline) as well as after 7, 15 and 30 days.

Statistical assessment:

The equivalence between the groups of the main objective criteria will be assessed in a confirmatory way at the end of the treatment, unilaterally by means of the SSSP.

Introduction The CDC (Centers for Disease Control and Prevention) is responding to an outbreak of respiratory disease caused by a new coronavirus that was first detected in China and has now been detected in almost 90 locations worldwide, including in the United States. The virus has been termed "SARS-CoV-2" and the disease causing it has been termed "coronavirus disease 2019" (abbreviated "COVID-19").

The current covid19 pandemic is a situation that: is severe, unusual, or unexpected; it has implications for public health beyond the national border of the affected State; and requires immediate international action.

For the same reason, it is urgent to look for routes that can contribute something new, hopefully fast, effective and economic that will solve or mitigate the current pandemic.

In this work we will use the bases of translational medicine to bring conventional medicine, studies and treatment that are born from the terrain of diverse therapeutic possibilities.

PROBLEM STATEMENT

Description of the problem Covid-19 is an infectious disease caused by the SARS-CoV-2 virus. It was first detected in the Chinese city of Wuhan (Hubei province) in December 2019. In three months it spread to practically every country in the world, which is why the World Health Organization declared it a pandemic.

There is no known effective treatment for the disease. The WHO recommends that randomized controlled trials be conducted with volunteers to test the effectiveness and safety of some potential treatments.

Based on this, we look at research processes given in the past to carry out (initial translational medicine) those promising and initial observations in infectious treatment to covid treatment 19 .

Delimitation of the Problem it was considered that the research that could really contribute to addressing the problem previously raised, should be directed to the development of a drug proposal of therapeutic possibilities studied in the past, based on both conventional and unconventional research.

General and specific research objectives

General purpose :

To determine the effectiveness of oral chlorine dioxide in the treatment of COVID 19

Specific objectives :

1. Measure the positivity or negativity of COVID 19 in patients who received treatment with chlorine dioxide.

2. Determine the clinical improvement based on the VAS visual scale.

Expected results :

What is expected is to reduce morbidity and especially mortality from viral infection of COVID, through management with chlorine dioxide.

Research Question

In this way, starting from the delimitation of the problem, the following research question is posed:

Could the use of chlorine dioxide modify morbidity and mortality in patients infected with COVID 19?

JUSTIFICATION Given the avalanche of deaths caused by the coronavirus in the absence of truly effective treatment, we have developed a protocol for dealing with COVID infection, particularly in hospitalized patients and in the ICU, with the aim of trying to reduce the morbidity and mortality of the Viral infection.

, we recommend a complementary experimental and exploratory approach that seeks to reduce the destructive and fibrotic effects of the process , as well as the storm. leukocyte and antiphospholipid syndrome that occurs in many cases and in other cases prevent, while reducing, the recovery times of patients.

State of the art at the international level in research treatments against coronavirus • Vaccines Three vaccination strategies are being investigated. First, the researchers aim to build a complete virus vaccine. T. A second strategy, subunit vaccines, aims to create a vaccine that sensitizes the immune system to certain virus subunits. . A third strategy is nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a vaccine). Experimental vaccines of any of these strategies would have to be tested for safety and efficacy. It is likely to take months to a year to achieve a truly efficient vaccine. The mutagenicity of the virus makes it difficult.

Antivirals On January 23, Gilead Sciences was in communication with researchers and physicians in the United States and China about the ongoing outbreak of the Wuhan coronavirus and the potential use of Remdesivir as an investigational treatment.

In late January, the Russian Ministry of Health identified three adult medications that could help treat the disease. They are ribavirin, lopinavir / ritonavir, and interferon beta-1b. These drugs are commonly used to treat hepatitis C, HIV infection, and multiple sclerosis, respectively. The ministry provided Russian hospitals with descriptions and guides on the mechanism of action of the treatment and the recommended doses. In February, China started using triazavirin, a 2014 drug developed in Russia, with the aim of testing whether it is effective in controlling the disease. This drug was created at the Ural Federal University in Yekaterinburg to treat H5N1 flu (avian flu). It has been used against COVID-19 due to the similarity between the two diseases. On March 18 an article reports that lopinavir / ritonavir treatment is negative in clinical trials with 199 patients in China. There are no benefits.

Chinese researchers discovered that Arbidol, an antiviral drug used to Treating the flu could be combined with Darunavir, a medicine used in the treatment of HIV, to treat patients with coronavirus.

Chloroquine phosphate has shown apparent efficacy in the treatment of COVID-19 associated pneumonia. In clinical trials with 100 patients, it was found to be superior to control treatment to inhibit exacerbation of pneumonia, improve lung imaging findings, promote negative virus conversion, and shorten disease. chloroquine could prevent orf1ab, ORF3a, and ORF10 from attacking heme to form porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to some extent.

The National Center for Biotechnology Development of China stated on March 17 that the antiviral Favipiravir, an RNA polymerase inhibitor, showed positive results in a case-control study of 80 patients at Shenzhen People's Hospital No. 3, The who received Favipiravir treatment tested negative within a shorter period of time compared to the control group, and recommends that it be included in treatment.

Hydroxychloroquine, a less toxic derivative of chloroquine, would be more potent in inhibiting SARS-CoV-2 infection in vitro. On March 16, 2020, a leading French authority and French Government advisor on COVID-19, Professor Didier Raoult of the Instituto University Hospital Institute of Infectious Diseases (IHU-Méditerranée infection) in Marseille (Bouches-du-Rhône, Provence-Alpes-Côte d 'Azur), announced that a trial with 24 patients from southeastern France had shown that chloroquine is a treatment effective for COVID-19. 600 mg of hydroxychloroquine (brand name Plaquenil) were administered to these patients every day for 10 days.

- Against the cytokine storm Tocilizumab has been included in the treatment guidelines by the China National Health Commission after a small study was completed. In combination with an analysis of Serum ferritin blood to identify cytokine storms is intended to counteract such developments, which are believed to be the cause of death in some affected individuals. The interleukin-6 receptor antagonist was approved by the FDA for treatment of cytokine release syndrome induced by a different cause, CAR T cell therapy, in 2017.

- Passive antibody therapy The use of blood donations from healthy people who have already recovered from COVID-19 is being investigated, a strategy that has also been tested for SARS, a previous cousin of COVID-19. The mechanism of action is that antibodies naturally produced in the immune system of those who have already recovered are transferred to people who need them through a non-vaccine-based form of immunization.

Vir Biotechnology, based in San Francisco, is evaluating the effectiveness of previously identified monoclonal antibodies (mAbs) against the virus.

Researchers from Utrecht University and Erasmus MC announced that they found a human monoclonal antibody that blocks SARS-CoV-2 infection.

A systematic search of the use of chlorine dioxide in the international bibliography for indexed literature was made .The most significant findings in the bibliography referenced above is that they are focused on disinfection of areas, use in oral health, use in agronomy and a phase 1 study in rats with Influenza A-induced infection in two groups, one treated with chlorine dioxide and the other without chlorine dioxide.

THEORETICAL FRAMEWORK CHLORINE DIOXIDE AND THE BASES OF ITS THERAPEUTIC APPLICATION

The therapeutic action of chlorine dioxide is given by its selectivity for pH. It means that this molecule dissociates and releases oxygen when it comes in contact with another acid. When reacting, it is converted to sodium chloride (common salt) and at the same time it releases oxygen, which in turn oxidizes (combusts) the pathogens (harmful germs) of acidic pH, converting them into alkaline oxides ("ashes"). Therefore, as chlorine dioxide dissociates, it releases oxygen in the blood, as do erythrocytes (red blood cells) through the same principle (known as the Bohr effect), which is to be selective for acidity. Like blood, chlorine dioxide releases oxygen when it encounters acidity, either from lactic acid or from the acidity of the pathogen. Its therapeutic effect is due, among others, to the fact that it helps in the recovery of many types of diseases, creating an alkaline environment, at the same time eliminating small acid pathogens, in my opinion, through oxidation, with an impossible electromagnetic overload to dissipate by unicellular organisms.

Multicellular tissue has the ability to dissipate this charge and is not affected in the same way.

Biochemistry, in turn, defines cell protection through hydrogen sulfide groups. Chlorine dioxide, which is the second strongest disinfectant known after ozone, is much more indicated for therapeutic use since it is also capable of penetrating and eliminating biofilm, something that ozone does not do. The great advantage of the therapeutic use of Chlorine dioxide is the impossibility of bacterial resistance to ClO2. Chlorine dioxide is a selective oxidant and unlike other substances it does not react with most components of living tissue. Chlorine dioxide does react quickly with phenols and thyroles essential for bacterial life. In phenols, the mechanism is to attack the benzene ring, eliminating odor, taste and other intermediate compounds. Chlorine dioxide removes viruses effectively and is up to 10 times more effective Evaluation of the antiviral activity of chlorine dioxide against feline calicivirus, human influenza virus, measlesvirus, canine distemper virus, human herpesvirus, human adenovirus, canine adenovirus and canine parvovirus. It also proved to be highly effective against small parasites, the protozoa.

A subject of great concern to medical professionals in medical scientific terms is the reactivity of chlorine dioxide with essential amino acids. In some tests on the reactivity of chlorine dioxide with 21 essential amino acids, only cysteine , Tryptophan and tyrosine , proline and hydroxyproline were reactive at a pH around 6. . These amino acids are relatively easy to replace.

Cysteine and Methionine . Oxidation by chlorine dioxide of methionine and cysteine derivatives to sulfoxide they are two aromatic amino acids that contain sulfide, tryptophan and tyrosine and the 2 inorganic ions FE2 + and Mn2 +. Cysteine, due to its membership in the thiol group, is an amino acid up to 50 times more reactive with all microbe systems than the other four essential amino acids, and therefore unable to create resistance against chlorine dioxide. Although it is not scientifically proven to date, pharmacodynamics usually assumes that the cause of its antimicrobial effect is due to its reactions to the four amino acids listed above or to protein and peptide residues.

1. Chlorine dioxide is a yellow gas that dissolves easily in water, without altering its structure.

2. It is obtained by mixing sodium chlorite and dilute hydrochloric acid.

2. The chlorine dioxide gas dissolved in water is an oxidant 3. Chlorine dioxide is pH selective and the more acidic the pathogen, the stronger the reaction.

4. According to toxicological studies by the EPA (US Environmental Protection Agency), chlorine dioxide does not leave residues, nor does it accumulate in the body in the long term.

5. In the oxidation process it is converted to oxygen and sodium chloride (common salt).

CHLORINE DIOXIDE AND THE BASES OF ITS THERAPEUTIC APPLICATION IN CORONAVIRUSES Chlorine dioxide (ClO 2) has been used for over 100 years to fight all kinds of bacteria, viruses, and fungi. It acts as a disinfectant, since in its mode of action it turns out to be an oxidant. It closely resembles the way our own body works, for example in phagocytosis, where an oxidation process is used to eliminate all kinds of pathogens. Chlorine dioxide (ClO 2) is a yellowish gas that, to date, has not been introduced into the conventional pharmacopoeia as an active ingredient, although it is compulsory used to disinfect and preserve blood bags for transfusions. It is also used in the majority of bottled waters suitable for consumption, since it leaves no toxic residues; in addition to being a very soluble gas in water and that evaporates from 11 ºC.

The recent pandemic of the Covid-19 coronavirus demands urgent solutions with an approach with all possible approaches, whether conventional or alternative. In previous investigations, chlorine dioxide (ClO 2) in aqueous solution at low doses eliminated this virus.

The approach is as follows: on the one hand we know that viruses are absolutely sensitive to oxidation and therefore, it is used in human blood bags against viruses such as HIV and studies in rats reveal that it completely controls virus infections Influenza A, it is proposed that it should also act on SARS -Cov -2.

Base proposals for mechanisms of action in COVID 19

1. Chlorine dioxide removes viruses through the selective oxidation process in a very short time. It does this by denaturing the capsid proteins, and subsequently oxidizes the genetic material of the virus, disabling it. A completely new approach that has been studied by Andreas Ludwig Kalcker, one of the members of this research team, for more than thirteen years with the result of three pharmaceutical patents for parenteral use. It can be produced by any pharmacy as a master preparation and has been used in a similar way to (DAC N-055) in the old German Drug Code as "Natrium Chlorosum" since 1990.

Until now solutions have been proposed that result in extremely slow processes, and given the rate of attack of the virus, we must try to use the fastest and most expeditious routes possible. The great advantage of chlorine dioxide is that it works for any viral subspecies and there are no possible resistances to this type of oxidation. Let's not forget that this substance has been used for 100 years in wastewater without generating any type of resistance.

2. There is already scientific evidence that chlorine dioxide is effective in SARS-CoV-2 coronaviruses, It has also been shown to be effective in human coronavirus and in animals such as dogs, known as canine respiratory coronavirus, or in cats, including feline enteric coronavirus (FECV) and the better known virus of feline infectious peritonitis (FIPV), since it denatures the capsids by oxidation inactivating the virus in a short time .

It should be noted that chlorine dioxide to ingest is a completely new antiviral approach as it is an oxidant and can eliminate by combustion any subspecies or mutant variant of virus. Given the emergency situation in which we currently find ourselves with Covid-19, the oral use of ClO2 is proposed immediately through a protocol already known and used.

2. Toxicity: The biggest problems that arise with medications in general are due to their toxicity and side effects. New studies demonstrate its viability. Although the toxicity of chlorine dioxide in case of massive inhalation is known, there is no clinically proven death even at high doses by oral ingestion. The lethal dose (LD50, acute toxicity ratio) is considered to be 292 mg per kilogram for 14 days, where its equivalent in a 50 kg adult would be 15,000 mg administered for two weeks of a gas dissolved in water (something almost impossible). The oral sub-toxic doses used are around 50 mg dissolved in 100 ml of water 10 times a day, which is equivalent to 0.5 g daily (and, therefore, only 1/30 of the LD50 of 15 g of ClO2 per day).

Chlorine dioxide dissociates, breaks down in the human body in a few hours into a negligible amount of common salt (NaCL) and oxygen (O2) within the human body. Furthermore, measurements of venous blood gases have indicated that it is capable of substantially improving the lung oxygenation capacity of the affected patient.

OPERATION CHLORINE DIOXIDE AGAINST VIRUSES As a general rule, most viruses behave similarly and once they bind to the appropriate host type - bacteria or cell, as the case may be - the nucleic acid component that the virus introduces takes over after protein synthesis processes in the infected cell. Certain segments of the viral nucleic acid are responsible for the replication of the genetic material of the capsid. In the presence of these nucleic acids, the CLO2 molecule becomes unstable and dissociates, releasing the resulting oxygen to the medium, which in turn helps to oxygenate the surrounding tissue, increasing the mitochondrial activity and, therefore, the response of the immune system. Nucleic acids, DNA-RNA, consist of a chain of puric and pyrimidine bases, see: guanine (G), cytosine (C), adenine (A) and thymine (T). It is the sequence of these four units along the chain that makes one segment different from another. The guanine base, which is found in both RNA and DNA, is very sensitive to oxidation, forming 8-oxoguanin as a by-product of it. Therefore, when the CLO2 molecule comes in contact with guanine and oxidizes it, it leads to the formation of 8-oxoguanin, thus blocking viral nucleic acid replication by base pairing. Although the replication of the protein capsid may continue; Fully functional virus formation is blocked by oxidation thanks to CLO2.

The CLO2 molecule has characteristics that make it an ideal candidate for treatment in the clinical setting, since it is a product with a high selective oxidation power and a great capacity to reduce acidosis, increasing oxygen in the tissues and mitochondria, thus facilitating the rapid recovery of patients with lung diseases.

POSSIBLE PRECAUTIONS AND CONTRAINDICATIONS Chlorine dioxide reacts with antioxidants and various acids, so the use of vitamin C or ascorbic acid is not recommended during treatment, as it nullifies the effectiveness of chlorine dioxide in the elimination of pathogens (the antioxidant effect of one prevents the selective oxidation of the other.) Therefore, it is not advisable to take antioxidants during the days of treatment. Stomach acid has been shown not to affect its effectiveness. In patients with Warfarin treatment, they should constantly check the values to avoid cases of overdose, as chlorine dioxide has been shown to improve blood flow. Although chlorine dioxide is very soluble in water, it has the advantage that it does not hydrolyze, so it does not generate toxic carcinogenic THM (trihalomethanes) such as chlorine. It also does not cause genetic mutations or malformations.

HYPOTHESIS Orally administered chlorine dioxide eliminates COVID infection 19. METHODOLOGY TYPE OF STUDY Observational, prospective, quasi-experimental study of a group of cases. Characteristics of our study: Like quasi-experimental studies, it is used, particularly, to determine the effect of treatments or interventions. It has two basic characteristics: the first, it does not require the randomization procedure for the formation of the study and control groups; the second may or may not have control groups. This quasi-experimental study offers an adequate level of internal and external validity. In addition, we will use time series without a control group, based on a single group that serves as study and control. Once established, periodic measurements of the dependent variable are carried out, then the treatment is applied and subsequently the dependent variable continues to be measured periodically.

Condition or disease
Condition or disease: COVID-19
Location
Colombia
Phase
-
Study design
Study type:Observational
Observational Model:Case-Only
Time Perspective:Prospective
Eligibility Criteria
Sexes Eligible for Study:All
Sampling method:Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/29/2020
First Posted: March/30/2020
Last Update Posted: March/30/2020
Sponsors: Estudios Clínicos Latino América
Status: Not yet recruiting
Description

Various anti-viral treatments are being tested in clinical trials worldwide. The World Health Organization launched a simple,pragmatic worldwide open-label trial to test Remdesivir, Lopinavir/Ritonavir, Interferon and Hydroxychloroquine or Chloroquine.The most important complication of COVID-19 severe cases is respiratory failure from severe acute respiratory syndrome (SARS), the leading cause of mortality. Accumulating evidence suggests that patients with severe COVID-19 might have a cytokine storm syndrome, a hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinemia and multiorgan failure.

The proposed pathophysiological mechanism of cytokine storm and inflammatory cascade activation is based on evidence collected primarily during the SARS-CoV and MERS-CoV epidemics (with a significant increase in IL1B, IL6, IL12, IFNγ, IP10, TNFα, IL15, and IL17 among others). The data collected during the pandemic with COVID-19 also shows a significant increase in inflammatory cytokines (GCSF, IP10, MCP1, MIP1A, and TNFα, among others) in sicker patients admitted to intensive care. In the absence of effective treatments for the management of patients with COVID-19 and respiratory failure, the immunomodulatory and anti-inflammatory effect of colchicine on cytokines involved in the hyper-inflammatory state is postulated. Several lines of research worldwide are testing powerful anti-inflammatory drugs for the pandemic, with different options including steroids, cytokine blockers, and other potent anti-inflammatory agents. Steroids are partially contraindicated in viral infections.

Colchicine is a powerful anti-inflammatory drug approved for the treatment or prevention of gout and Familial Mediterranean Fever at doses ranging between 0.3 mg and 2.4 mg/day. Its mechanism of action is through the inhibition of tubulin polymerization, as well as through potential effects on cellular adhesion molecules and inflammatory chemokines. It might also have direct anti-inflammatory effects by inhibiting key inflammatory signalling networks known as inflammasome and pro-inflammatory cytokines. Additionally, evidence suggests that colchicine exerts a direct anti-inflammatory effect by inhibiting the synthesis of tumor necrosis factor alpha and IL-6, monocyte migration, and the secretion of matrix metalloproteinase-9. Through the disruption of the cytoskeleton, colchicine is believed to suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. All these are potentially beneficial effects that might diminish or ameliorate the COVID-19 inflammatory storm associated with severe forms of the disease. Importantly, in one contemporary trial low-dose colchicine administered to patients who survived from acute coronary syndrome shows a statistically significantly reduction of cardiovascular complications.

We have therefore designed in a simple, pragmatic randomized controlled trial to test the effects of colchicine on severe hospitalized COVID-19 cases with the aim of reducing mortality.

Condition or disease
Condition or disease: COVID-19
Location
-
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: March/23/2020
First Posted: March/26/2020
Last Update Posted: April/14/2020
Sponsors: Gilead Sciences
Status: Available
Abstract

The primary objective of this study is to provide expanded access of remdesivir (RDV) for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.

Condition or disease
Condition or disease: SARS-CoV2 Infection
Location
France
Germany
Italy
Spain
Switzerland
United Kingdom
United States
Phase
-
Study design
-
Eligibility Criteria
Ages Eligible for Study:12 Years to 12 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:No
Clinical trial
Last Verified: March/31/2020
First Submitted: March/22/2020
First Posted: March/24/2020
Last Update Posted: April/13/2020
Sponsors: Oslo University Hospital
Status: Recruiting
Abstract

The (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.

Condition or disease
Condition or disease: SARS-CoV Infection; COVID 19; Acute Respiratory Distress Syndrome ARDS
Location
Norway
Phase
Phase 2/Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/16/2020
First Posted: March/18/2020
Last Update Posted: March/19/2020
Sponsors: Groupe Hospitalier Pitie-Salpetriere
Status: Recruiting
Abstract

The outbreak of Covid-19 started several clinical trials and treatment experiments all over the world in the first months of 2020. This study investigates reports of adverse events related to used molecules, including but not limited to protease inhibitors (lopinavir/ritonavir), chloroquine, azithromycin, remdesivir and interferon beta-1a. Analyses of reports also include the International classification of disease ICD-10 for treatments in the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database (VigiBase).

Condition or disease
Condition or disease: Coronavirus; Iatrogenic Disease; Acute Kidney Injury; ARDS, Human
Location
France
Phase
-
Study design
Study type:Observational
Observational Model:Case-Only
Time Perspective:Cross-Sectional
Eligibility Criteria
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/12/2020
First Posted: March/19/2020
Last Update Posted: March/24/2020
Sponsors: Institut National de la Santé Et de la Recherche Médicale, France
Status: Recruiting
Description

This study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments of COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC + Lopinavir/Ritonavir plus interferon ß-1a versus SoC + Hydroxychloroquine. Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is subject clinical status (on a 7-point ordinal scale) at day 15. The secondary objectives of the study are to evaluate 1) the clinical efficacy of different investigational therapeutics through 28 days of follow-up as compared to the control arm as assessed by clinical severity (7-point ordinal scale, national early warning score, oxygenation, mechanical ventilation), hospitalization, mortality through 28 days of follow-up, in-hospital mortality and 90-day mortality 2) the safety of different investigational therapeutics through 28 days of follow-up as compared to the control arm as assessed by the cumulative incidence of serious adverse events (SAEs), the cumulative incidence of Grade 3 and 4 adverse events (AEs), the discontinuation or temporary suspension of antiviral drugs (for any reason), and the changes in blood white cell count, haemoglobin, platelets, creatinine, blood electrolytes, prothrombine time and international normalized ratio (INR), glucose, total bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) over time.

Condition or disease
Condition or disease: Corona Virus Infection
Location
France
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/12/2020
First Posted: March/19/2020
Last Update Posted: April/2/2020
Sponsors: University Hospital, Akershus
Status: Recruiting
Description

Chloroquine is one of two therapeutics (in addition to remdesivir) that has demonstrated in vitro inhibitory effects on SARS-CoV-2 and the drug is immediately available from national pharmacies. No delay is accordingly expected in treatment initiation after study commencement. In light of the evidence supporting chloroquine as a promising therapeutic in patients with COVID-19, the expected impact of the current proposal is considerable both in the short- and long-term. If successful, treatment with chloroquine has the potential to be the first evidence based treatment for COVID-19. The drug is affordable and the risk of side effects is low, making it an attractive therapeutic in large proportions of the population on a global scale.

In the current proposal aims to investigate the virological and clinical effects of chloroquine treatment in patients with established SARS-CoV-2 in need of hospital admission. The investigators hypothesize that early treatment with chloroquine in patients with established COVID-19 is safe and will significantly improve prognosis and impact clinical outcomes. More specifically, the investigators hypothesize that early treatment with chloroquine will increase the virological clearance rate of SARS-CoV-2, and lead to more rapid resolve of clinical symptoms, decreased proportion of patients with clinical deterioration and a decreased admission rate to intensive care units and in-hospital mortality. Considering the immediate and worldwide health emergency associated with the SARS-CoV-2 outbreak and the current lack of evidence based medical interventions for this patient group, studies investigating such possible treatment modalities in COVID-19 are direly needed.

The study is a two-arm, open label, pragmatic randomized controlled trial (RCT) designed to assess the virological and clinical effect of chloroquine therapy in patients with established COVID-19. Pragmatic clinical trials are characterized by focus on informing decision-makers on optimal clinical medicine practice and an intent to streamline procedures and data collection in the trial. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), pragmatic clinical trials can include a larger number of patients at a short time duration and at a lower cost. Due to the immediate need for study commencement and the time frame of the current proposal, a pragmatic approach will enable swift initiation of randomization and treatment. Data will be extracted from the data warehouse at Akershus University Hospital for eligible patient identification (i.e. electronic surveillance) and for automatic data extraction to the study specific database. The study will not be able to procure an acceptable placebo treatment and the study will accordingly not be placebo-controlled.

All patients at Akershus University Hospital with suspicion of acute respiratory tract infections are examined with a nasopharyngeal swab, with subsequent microbiological examination, including SARS-CoV-2 specific RT-PCR. Participants will be recruited from the entirety of the inpatients at the participating hospitals. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly, with maximum interval 24 hours, for SARS-CoV-2 positive subjects.

The study aims to include patients by a sequential adaptive approach, where analyses are planned after the inclusion of 51 patients, with subsequent analyses after 101, 151 and 202 completed patients. All patients included in each sequence will be used for the final analyses of the entire study. This approach will enable frequent assessment of all outcome measures.

Data will be collected from the hospital electronic record system, including electronic patient records, laboratory and medical imaging systems, and prescribing systems. The data warehouse at Akershus University Hospital will be utilized for automatic data extraction to the study specific database. All clinical variables will be registered in the study eCRF system, including clinical endpoints and quantitative virological results from serial nasopharyngeal specimens.

Condition or disease
Condition or disease: Corona Virus Infection
Location
Norway
Phase
Phase 4
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: March/1/2020
First Posted: March/9/2020
Last Update Posted: April/9/2020
Sponsors: U.S. Army Medical Research and Development Command
Status: Available
Description

The treatment of communicable Novel Coronavirus (CODIV-19) of 2019 with Remdesivir (RDV; GS-5734™) also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Condition or disease
Condition or disease: Coronavirus Disease 2019
Location
-
Phase
-
Study design
-
Eligibility Criteria
Sexes Eligible for Study:All
Accepts Healthy Volunteers:No
Clinical trial
Last Verified: March/31/2020
First Submitted: February/27/2020
First Posted: March/2/2020
Last Update Posted: April/15/2020
Sponsors: Gilead Sciences
Status: Recruiting
Abstract

The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale on Day 11.

Condition or disease
Condition or disease: COVID-19
Location
China
France
Germany
Hong Kong
Italy
Japan
Korea, Republic of
Netherlands
Singapore
Spain
Sweden
Switzerland
Taiwan
United Kingdom
United States
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:12 Years to 12 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: February/27/2020
First Posted: March/2/2020
Last Update Posted: April/13/2020
Sponsors: Gilead Sciences
Status: Recruiting
Abstract

The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.

Condition or disease
Condition or disease: COVID-19
Location
France
Germany
Hong Kong
Italy
Korea, Republic of
Netherlands
Singapore
Spain
Switzerland
Taiwan
United Kingdom
United States
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:12 Years to 12 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: February/14/2020
First Posted: March/2/2020
Last Update Posted: March/2/2020
Sponsors: Tongji Hospital
Status: Not yet recruiting
Description

This study is a multi-center, randomized, open, blank-controlled, multi-stage clinical study. As there are no effective treatments, the project team will evaluate possible treatments (including but not limited to interferon α) based on actual conditions. , Lopinavir / ritonavir, remdesivir, single / polyclonal antibodies against coronavirus), explore the most effective antiviral treatment options.

The first phase will assess the efficacy and safety of interferon alpha compared to standard treatment for approximately 328 hospitalized adult patients diagnosed with a new coronavirus infection in Wuhan.

Patients with COVID-19 within 7 days of onset of symptoms were screened and randomly assigned as soon as possible after screening (within 24 hours). Patients will be allocated in a 1: 1 ratio, receiving the interferon alpha treatment group or only the standard treatment group. Patients who do not meet the inclusion and exclusion criteria are only allowed to be re-screened once, provided that the time from symptom onset to randomization remains within 7 days.

This study planned to randomize approximately 328 adult subjects. It will be stratified according to whether the onset time is ≤ 3 days, and randomly divided into groups of 1: 1, receiving standard treatment or interferon alpha atomization twice a day, 1 stick (10ug) each time, treatment course For 10 days. Subjects and all research center staff were not blinded.

The primary endpoint of this study was the incidence of side effects within 14 days of enrollment. Therefore, a 14-day visit is essential for the data needed for this endpoint. Every effort should be made to ensure that this study visit is completed in a timely manner.

Out-of-hospital treatment or discharge will reach the discharge standard on the day of implementation and will be implemented in accordance with the Health and Medical Commission's "Unknown Viral Pneumonia Diagnosis and Treatment Plan (Trial)". For patients treated outside the hospital or who have been discharged, final assessments are performed by phone and using a questionnaire (if applicable).

Condition or disease
Condition or disease: COVID-19; Recombinant Human Interferon α1β
Location
-
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: January/31/2020
First Submitted: February/9/2020
First Posted: February/24/2020
Last Update Posted: February/24/2020
Sponsors: Huilan Zhang
Status: Recruiting
Description

This study is a multi-center, randomized, open, blank-controlled, multi-stage clinical study. As there are no effective treatments, the project team will evaluate possible treatments (including but not limited to Pirfenidone) based on actual conditions. Ketone, Pirfenidone, lopinavir / ritonavir, remdesivir, single / polyclonal antibodies against coronavirus), explore the most effective treatment options.

The first phase will assess the efficacy and safety of approximately 147 (primarily estimated) hospitalized adult patients diagnosed with Wuhan new coronavirus infection in the pirfenidone-treated group compared to standard treatment.

Patients with influenza within 14 days of onset of symptoms were screened and randomly assigned as soon as possible after screening (within 4 day). Patients will be allocated in a 1: 1 ratio and divided into the pirfenidone treatment group or the standard treatment group only. Patients who do not meet the inclusion and exclusion criteria are only allowed to be re-screened once, provided that the time from onset of symptoms to randomization remains within 14days.

This study planned to randomize approximately 147 adult subjects. They will be stratified according to whether the onset time is ≤ 14 days and randomly divided into groups of 1: 1, receiving standard treatment or pirfenidone orally 3 times a day, 2 tablets each time. The course is 4 weeks or more. Subjects and all research center staff were not blinded.

Study selection criteria: (1) Age ≥ 18 years. (2) Clinically diagnosed patients with new type of coronavirus pneumonia include: on the basis of meeting the criteria for suspected cases, one of the following pathogenic evidence: ① real-time fluorescent RT-PCR of respiratory specimens or blood specimens for detection of new coronavirus nucleic acid; Respiratory or blood specimens are genetically sequenced and highly homologous to known new coronaviruses. (3) The time interval between the suspected neocoronary pneumonia pneumonia case and the random enrollment is determined within 4 days to 7 days according to the history symptoms and chest CT imaging. Cough, diarrhea, or other related symptoms can be used. The imaging changes are mainly based on chest CT.

Study exclusion criteria: (1) AST and ALT> 1.5 x ULN at visit 1; (2) bilirubin> 1.5 x ULN at visit 1; (3) Cockcroft-Gault formula at visit 1 Calculated creatinine clearance rate <30 mL / min; (4) patients with potential chronic liver disease (Child Pugh A, B or C liver injury; (5) previous treatment with nidanib or pirfenidone; Screening visit (Visit 1) 1 month or 6 half-life (whichever is greater) received other research drug treatment; (7) Based on ATS / ERS / JRS / ALAT 2011 guidelines (P11-07084) IPF diagnosis; (8) Obvious pulmonary hypertension (PAH) defined by any of the following standards: ① Clinical / echocardiographic evidence of previously obvious right heart failure; ② Medical history including right heart catheter showing a heart index ≤ 2l / min / m2; ③ required Parenteral administration of epoprostenol / treprostinil for the treatment of PAH; (9) other clinically significant pulmonary abnormalities considered by the investigator; (10) major extrapulmonary physiological limitations (such as chest wall deformities, large amounts Pleural effusion); (11) cardiovascular disease, any of the following diseases: ① severe hypertension within 6 months of visit 1, treatment Uncontrollable (≥160 / 100 mmHg); ② myocardial infarction within 6 months of visit 1; ③ unstable angina within 6 months of visit 1; (12) history of severe central nervous system (CNS) events; (13) Known allergies to the test drug; (14) Other diseases that may interfere with the testing process or judged by the investigator may interfere with the trial participation or may put the patient at risk when participating in the trial; (15) pregnancy, Women who are breastfeeding or planning a pregnancy; (16) Patients are unable to understand or follow the test procedures, including completing the questionnaires themselves without help.

Study design primary and secondary endpoints Main endpoints: (1) Absolute changes in baseline lesion area, finger pulse oxygen, and blood gas from baseline at 4 weeks of chest CT images; (2) Total score of King's Interstitial Lung Disease Short Questionnaire (K-BILD) at Week 4 Absolute change from baseline.

Secondary end point: Time to death within 4 weeks due to respiratory causes; time to disease progression or death within 4 weeks; recovery of blood routine lymphocytes at week 4; and blood inflammation indicators at week 4 ( IL-8, etc.); at week 4, absolute changes in viral nucleic acid from baseline; at week 4, pulmonary fibrosis survival symptoms dyspnea scores absolute changes from baseline; at week 4, pulmonary fibrosis survival Symptoms of cough scores are absolute changes from baseline.

Condition or disease
Condition or disease: Novel Coronavirus Pneumonia; Pneumonia; Pirfenidone
Location
China
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: January/30/2020
First Posted: February/4/2020
Last Update Posted: April/14/2020
Sponsors: Capital Medical University
Status: Suspended
Description

In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay.

Whilst the outbreak is likely to have started from a zoonotic transmission event associated with a large seafood market that also traded in live wild animals, it soon became clear that person-to-person transmission was also occurring. The number of cases of COVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally. Mathematical models of the expansion phase of the epidemic suggested that sustained person-to-person transmission is occurring, and the R-zero is substantially above 1, the level required for a self-sustaining epidemic in human populations.

The clinical spectrum of COVID-19 appears to be wide, encompassing asymptomatic infection, a mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and even death. Although the per infection risk of severe disease remains to be determined, and may differ from the initial reports of 10-15%, the large number of cases in Wuhan has resulted in a large number of patients hospitalised with pneumonia. Progression from prodromal symptoms (usually fever, fatigue, cough) to severe pneumonia requiring supplementary oxygen support, mechanical ventilation, or in some cases ECMO appears to occur most commonly during the second week of illness in association with persistent viral RNA detection. This provides a window of opportunity to test candidate antiviral therapeutics.

This new coronavirus, and previous experiences with SARS and MERS-CoV, highlight the need for therapeutics for human coronavirus infections that can improve clinical outcomes, reduce risk of disease progression, speed recovery, and reduce the requirements for intensive supportive care and prolonged hospitalisation. In addition, treatments for mild cases to reduce the duration of illness and infectivity may also be of value were COVID-19 to become pandemic and/or endemic in human populations.

Given no specific antiviral therapy for COVID-19 and the availability of remdesvir as a potential antiviral agent based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with mild or moderate COVID-19.

Condition or disease
Condition or disease: COVID-19; SARS-CoV-2
Location
China
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: January/30/2020
First Posted: February/5/2020
Last Update Posted: April/14/2020
Sponsors: Capital Medical University
Status: Terminated
Description

In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay.

Whilst the outbreak is likely to have started from a zoonotic transmission event associated with a large seafood market that also traded in live wild animals, it soon became clear that person-to-person transmission was also occurring. The number of cases of infection with COVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally. Mathematical models of the expansion phase of the epidemic suggested that sustained person-to-person transmission is occurring, and the R-zero is substantially above 1, the level required for a self-sustaining epidemic in human populations.

The clinical spectrum of COVID-19 illness appears to be wide, encompassing asymptomatic infection, a mild upper respiratory tract infection, and severe viral pneumonia with respiratory failure and even death. Although the per infection risk of severe disease remains to be determined, case-fatality risk of 11-14% has been reported in several initial studies of seriously ill patients and case-fatality has been estimated approximately at 2% overall. Also the large number of cases in Wuhan has resulted in a large number of patients hospitalised with pneumonia requiring supplemental oxygen and sometimes more advance ventilator support.

This new coronavirus, and previous experiences with SARS and MERS-CoV, highlight the need for therapeutics for human coronavirus infections that can improve clinical outcomes, speed recovery, and reduce the requirements for intensive supportive care and prolonged hospitalisation.

Given no specific antiviral therapy for COVID-19 and the ready availability of remdesvir as a potential antiviral agent, based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with severe COVID-19.

Condition or disease
Condition or disease: COVID-19; Remdesivir; SARS-CoV-2
Location
China
Phase
Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: October/10/2019
First Submitted: October/23/2018
First Posted: October/24/2018
Last Update Posted: October/20/2019
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID)
Status: Recruiting
Description

Species Zaire ebolaviruses (EBOV) are members of the Filoviridae and are known primarily as the underlying cause of severe viral hemorrhagic fevers with disturbingly high case fatality rates. Between 1994 and the present, there have been many filovirus outbreaks affecting mostly central Africa, with 2 large outbreaks in 1995 in Kikwit, Democratic Republic of Congo (DRC), and in Gulu, Uganda in 2000-2001. The 2013-2016 West African outbreak significantly exceeded all previous outbreaks in geographic range, number of patients affected, and in disruption of typical activities of civil society. In 2018 there have been two additional outbreaks of EBOV infection, both in the Democratic Republic of the Congo and constituting the 9th and 10th recorded outbreaks of this infection in that country. The 10th outbreak is currently ongoing in the DRC as of December 2018 and has raised great concern because of the potential to expand greatly in scope and to spread to surrounding regions.

It has been suggested that one of the most important elements necessary to improve survival from Ebola virus infection is the provision of supportive care inclusive of hemodynamic support in the form of aggressive fluid replacement, ability to diagnose and correct severe metabolic derangements, early treatment of sepsis, and other standards of modern medical care. A small number of investigational therapeutics have been developed as putative antiviral strategies for treating this infection. Unfortunately, phase 1/2 data supporting the safety and efficacy of these agents are often limited, and thus there remains some degree of equipoise as to which of these interventions should be prioritized in the treatment of severe infection. The triple monoclonal antibody product ZMapp was studied through a randomized controlled trial (RCT) in the 2014-2016 West African outbreak and remains perhaps the best characterized of the available investigational products, but the end of that outbreak forced the RCT to close prior to crossing pre-specified evidentiary boundaries.

A WHO Research and Development Ebola Therapeutics Committee has agreed that, given the lethality of Ebola virus and the combination of human and non-human primate (NHP) efficacy data for ZMapp, either ZMapp+oSOC or oSOC alone could potentially be positioned as the control arm in comparative trials depending upon the preferences of the host countries. The DRC has chosen to use ZMapp + oSOC in the current protocol. However, both the nature and number of control and invegstigational arms may change over the course of the trial. Such changes would require protocol amendments.

This multicenter, multi-outbreak, randomized controlled trial will study the comparative safety and efficacy of additional investigational therapeutics compared to ZMapp in patients with known EBOV disease (Zaire) receiving oSOC. The primary endpoint of this comparison will be mortality by Day 28, with a number of secondary endpoints also planned that should generate important knowledge about the safety, ease of administration, and antiviral activity of all of these investigational interventions.

Condition or disease
Condition or disease: Ebola Virus
Location
Congo, The Democratic Republic of the
United States
Phase
Phase 2/Phase 3
Study design
Study type:Interventional
Eligibility Criteria
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: April/12/2020
First Posted: April/14/2020
Last Update Posted: April/14/2020
Sponsors: Hackensack Meridian Health
Status: Recruiting
Description

The principle objective of this observational database is to build research-grade real world data that will serve as platform to advance the scientific understanding and clinical care of patients with COVID-19.

1. Demographic, diagnostic, treatment and outcome data from centers throughout the Hackensack Meridian Health Network will be abstracted from the electronic health records of patients with confirmed or suspected COVID-19. This will be purely observational and no direction as to the care of the patient will be performed as part of this effort.

1a. Data points to be collected will include, but are not limited to: age, gender, zip code, prior evaluation for COVID-19, tobacco history, race, site of care, healthcare worker, nursing home care, visits to ER, presenting features of fever/ cough/ dyspnea/ gastrointestinal/ mental status changes, days of symptoms, comorbidities, uses of antihypertensives, duration of hospitalization/ icu care, presenting laboratory functions, presenting vital signs, need for oxygen support, dialysis/ ecmo use, treatment with hydroxychloroquine/ azithromycin/ remdesevir/ tociluzimab/ anti-inflammatory agents, arrhythmias/ QTc prolongation, enrollment on clinical trial, positive cultures, survival and cause of death. Additional data points will be added as needed.

2. The data will be entered into a central "Universal" database hosted within the REDCap system (HIPAA compliant, secure, access only per HMH research approval)

3. A de-identified dataset will be sent to COTA for primary statistical analysis as requested by the research teams. COTA will also make available a data/analytic visualization tool (hosted on Tableau) for analysis by primary investigators.

4. Additional data points and analysis may be added to the Universal database as requested by HMH investigators with IRB approval. De-identified data may also be sent directly to HMH investigators for their own analysis with IRB approval of their projects 5. Data will be made available to governmental agencies as requested.

Condition or disease
Condition or disease: COVID-19
Location
United States
Phase
-
Study design
Study type:Observational [Patient Registry]
Observational Model:Case-Only
Time Perspective:Prospective
Eligibility Criteria
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/18/2020
First Posted: March/23/2020
Last Update Posted: March/23/2020
Sponsors: Neuromed IRCCS
Status: Not yet recruiting
Description

Background Very recent evidences support the hypothesis that the novel coronavirus 2019 (2019-nCoV) uses the SARS-1 coronavirus receptor ACE2 for gains entry into target cells. Angiotensin receptor-blocker (ARB) drugs, one of the most commonly used antihypertensive drug, typically increase ACE2 expression, often very markedly. With SARS-CoV-2 infection increased ACE2 expression very definitely would not be beneficial, and could be adverse. However, augmented ACE2 expression with ARBs has been demonstrated in the kidneys and heart but has not been tested in the lungs. So, the hypothesis that using of ARBS or ACE inhibitors (ACE-I) drugs during the COVID-19 may possibly be harmful is urgently to be verified in epidemiological studies.

Aim To retrospectively test whether 2019-nCoV patients treated with ARB or ACE-I, in comparison with patients who not, are at higher risk of having severe COVID-19 (including death).

Population Hospitalized patients with confirmed COVID-19 infection (any type).

Outcome The project will retrospectively collect data on the most severe manifestation of COVID-19 occurred in 2019-nCoV infected patients during hospitalization. Severity will be classified as: hospital discharge with healing, asymptomatic, mild complications but not pneumonia, not severe pneumonia, severe pneumonia, acute respiratory distress syndrome (ARDS) and death. Classification of pneumonia will follow WHO criteria. Data on severity will be obtained from medical record at one-point time (at the moment of inclusion in the study).

Exposure Treatment for ARB or ACE-I. When available, type of drugs will be recorded.

Study design Patients will be divided in two groups, a) controls: individuals who did not develop severe COVID-19 respiratory disease (including individuals who recovered from the infection) and b) cases: individuals who developed severe COVID-19 disease (including fatal events). Association between use of ACE-I or ARB and severity of COVID-19 will be assessed by using of multivariable logistic regression analysis. Data on potential confounders will be obtained by medical records: age, sex, time intervals from hospital admission to worse manifestation of COVID-19 and to eventual death or recovering, smoking, body mass index, history of myocardial infarction, diabetes, hypertension, cancer, respiratory disease, other morbidities, creatinine, insulin, glomerular filtration rate together with use of Tocilizumab, anti-aldosterone agents, diuretics, Kaletra, cortisone, Remdesevir, Chloroquine, Sacubitril or Valsartan.

Condition or disease
Condition or disease: COVID-19
Location
Italy
Phase
-
Study design
Study type:Observational
Observational Model:Case-Control
Time Perspective:Retrospective
Eligibility Criteria
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes