Trial of Treatments for COVID-19 in Hospitalized Adults (DisCoVeRy)

Trial of Treatments for COVID-19 in Hospitalized Adults (DisCoVeRy)

Brief Summary:
This study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for 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 (this treatment arm has been ceased since June 29, 2020) + Lopinavir/Ritonavir plus interferon ß-1a versus SoC (this treatment arm has been ceased since June 29, 2020) + Hydroxychloroquine (this treatment arm has been ceased since May 24, 2020). 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 the subject clinical status (on a 7-point ordinal scale) at day 15.

Detailed 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 (this treatment arm has been ceased since June 29, 2020) + Lopinavir/Ritonavir plus interferon ß-1a versus SoC (this treatment arm has been ceased since June 29, 2020) + Hydroxychloroquine (this treatment arm has been ceased since May 24, 2020). 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.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 3100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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.
Masking: None (Open Label)
Masking Description:
- 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

Primary Purpose: Treatment
Official Title: Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults
Actual Study Start Date: March 22, 2020
Estimated Primary Completion Date: March 2023
Estimated Study Completion Date: March 2023

Arm:
- Experimental: Remdesivir
- Experimental: Lopinavir/ritonavir (stopped on June 29, 2020)
- Experimental: Lopinavir/ritonavir plus Interferon ß-1a (stopped on June 29)
- Experimental: Hydroxychloroquine (stopped on May 24, 2020)
- Active Comparator: Standard of care

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