Last Verified: | February/29/2020 |
First Submitted: | March/12/2020 |
Estimated Enrollment Submitted: | March/17/2020 |
First Posted: | March/19/2020 |
Last Update Submitted: | July/19/2020 |
Last Update Posted: | July/21/2020 |
Actual Study Start Date: | March/21/2020 |
Estimated Primary Completion Date: | February/28/2023 |
Estimated Study Completion Date: | February/28/2023 |
Study Type: | Interventional |
Allocation: | Randomized |
: | From March 22, 2020 to May 24, 2020, the study randomized participants 1:1:1:1:1 to standard of care alone (control) or with investigational product added. From May 24, 2020 to June 29, 2020, the study randomized participants 1:1:1:1 to standard of care alone (control) or with investigational product added. Since June 29, 2020, the study will randomize participants 1:1 to standard of care alone (control) or with investigational product added. If additional arms are added to or dropped from the trial, randomization will proceed with an equal probability of assignment to each of the remaining arms. |
Primary Purpose: | Treatment |
Masking: | None (Open Label) |
: | the treatment arm SOC + hydroxychloroquine has been ceased since May 24, 2020; the treatment arm SOC + lopinavir / Ritonavir and lopinavir / ritonavir + interferon ß-1a has been ceased since June 29, 2020 |
Arm | Intervention/treatment |
---|---|
Experimental: Remdesivir Remdesivir will be administered as a 200 mg intravenous loading dose on Day 1, followed by a 100 mg once-daily intravenous maintenance dose for the duration of the hospitalization up to a 10 days total course. n=620 | Drug: Remdesivir The lyophilized formulation of Remdesivir is a preservative-free, white to off-white or yellow, lyophilized solid containing 100 mg of Remdesivir to be reconstituted with 19 mL of sterile water for injection and diluted into IV infusion fluids prior to IV infusion. Following reconstitution, each vial contains a 5 mg/mL Remdesivir concentrated solution with sufficient volume to allow withdrawal of 20 mL (100 mg of remdesivir). It is supplied as a sterile product in a single-use, 30 mL, Type 1 clear glass vial. |
Experimental: Lopinavir/ritonavir (stopped on June 29, 2020) Lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered every 12 h for 14 days in tablet form. For patients who are unable to take medications by mouth, the lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered as a 5-ml suspension every 12 h for 14 days via a pre-existing or newly placed nasogastric tube. n=620 | |
Experimental: Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29) Lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered every 12 h for 14 days in tablet form. For patients who are unable to take medications by mouth, the lopinavir/ritonavir (400 lopinavir mg/100 mg ritonavir) will be administered as a 5-ml suspension every 12 h for 14 days via a pre-existing or newly placed nasogastric tube. Interferon ß1a will be administered subcutaneously at the dose of 44 µg for a total of 3 doses in 6 days (day 1, day 3, day 6). n=620 | Drug: Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29) IFN-ß-1a is supplied as a sterile solution containing no preservative available in a prefilled syringe. It will be provided as a single-dose prefilled graduated syringe with 44 µg per 0.5 mL. The liquid should be clear to slightly yellow. Do not use if the liquid is cloudy, discolored or contains particles. Use a different syringe. |
Experimental: Hydroxychloroquine (stopped on May 24, 2020) Hydroxychloroquine will be administered orally as a loading dose of 400 mg twice daily for one day followed by 400 mg once daily for 9 days. The loading dose of hydroxychloroquine through a nasogastric tube will be increased to 600 mg twice a day for one day, followed by a maintenance dose of 400 mg once a day for 9 days n=620 | Drug: Hydroxychloroquine (stopped on May 24, 2020) Hydroxychloroquine is supplied as film-coated 200 mg tablets. Hydroxychloroquine sulfate tablets are presented as white or whitish, peanut-shaped, oblong or round film-coated tablets containing 200 mg of hydroxychloroquine sulfate (equivalent to 155 mg base). |
Active Comparator: Standard of care Standard of care. n=620 |
Ages Eligible for Study: | 18 Years to 18 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Criteria: | Inclusion Criteria: - Adult ≥18 years of age at time of enrolment. - Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 72 hours prior to randomization. - Hospitalized patients with illness of any duration, and at least one of the following: - Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, OR - Acute respiratory failure requiring mechanical ventilation and/or supplemental oxygen. - Women of childbearing potential must agree to use contraception for the duration of the study. Acceptable birth methods control are listed in section 7.3 Exclusion Criteria: - Refusal to participate expressed by patient or legally authorized representative if they are present - Spontaneous blood ALT/AST levels > 5 times the upper limit of normal. - Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30 mL/min) - Pregnancy or breast-feeding. - Anticipated transfer to another hospital, which is not a study site within 72 hours. - Patients previously treated with one of the antivirals evaluated in the trial (i.e. remdesivir, interferon ß-1a, lopinavir/ritonavir, hydroxychloroquine) in the past 29 days - Contraindication to any study medication including allergy The following exclusion criteria are non applicable since lopinavir/ritonavir, lopinavir/ritonavir plus interferon ß-1a or hydroxychloroquine arm were stopped: - Use of medications that are contraindicated with lopinavir/ritonavir i.e. drugs whose metabolism is highly dependent on the isoform CYP3A with narrow therapeutic range (e.g. amiodarone, colchicine, simvastatine). - Use of medications that are contraindicated with hydroxychloroquine: citalopram, escitalopram, hydroxyzine, domperidone, pipéraquine. - Human immunodeficiency virus infection under highly active antiretroviral therapy (HAART). - History of severe depression or attempted suicide or current suicidal ideation |