An International Randomized Trial of Additional Treatments for COVID-19 in Hospitalized Patients Who Are All Receiving the Local Standard of Care - WHO-SOLIDARITY-GERMANY

Study Overview
=================
Brief Summary
-----------------
This study is an adaptive, randomized, open-label, controlled clinical trial, performed worldwide in collaboration with WHO and INSERM.

Official Title
-----------------
An International Randomized Trial of Additional Treatments for COVID-19 in Hospitalized Patients Who Are All Receiving the Local Standard of Care - WHO-SOLIDARITY-GERMANY

Conditions
-----------------
SARS-CoV-2 Infection, COVID-19, Moderate and Severe COVID-19

Intervention / Treatment
-----------------
* Other: Standard of Care (SoC)
* Drug: Remdesivir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients 18 years and older Current SARS-CoV-2 infection Admitted to the hospital ward or the ICU due to COVID-19 SpO2 <= 94% on room air OR oxygen demand OR breathing support Written informed consent obtained Exclusion Criteria: Patient's non-consent or inability to informed consent Pregnant or breastfeeding women. Subjects pretreated with one of the study drugs in the past 29 days Anticipated transfer within 72 hours to a non-study hospital Severe co-morbidity with life expectancy < 3 months AST or ALT > 5 times the upper limit of normal Stage 4 severe chronic kidney disease or requiring dialysis Contraindications and known intolerance to any of the study drugs Subjects participating in a potentially confounding drug or device trial Any reason why the patient should not participate (investigator's opinion)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard of Care (SoC)<br>This arm will receive standard supportive care according to guidelines for COVID-19. This is expected to vary regionally and may change throughout the trial based on new and emerging data on best care guidelines for patients. | Other: Standard of Care (SoC)<br>* Standard supportive care is expected to vary regionally and may change throughout the trial based on new and emerging data on best care guidelines for patients.<br>|
| Experimental: Remdesivir + SoC<br>Remdesivir 200 mg IV on day 1, followed by 100 mg IV daily infusion for 9 days plus optimized supportive care | Other: Standard of Care (SoC)<br>* Standard supportive care is expected to vary regionally and may change throughout the trial based on new and emerging data on best care guidelines for patients.<br>Drug: Remdesivir<br>* Remdesivir 200mg IV on day 1, followed by 100 mg IV daily infusion for 9 days or until discharge from hospital, whichever occurs first<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of clinical status on the ordinal 7-point severity-scale at day 15. | WHO 7-point ordinal scale: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death | at day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to an improvement of one category from admission using the 7-point ordinal scale |  | up to 29 days | 
| Mortality: 28 days mortality; in-house mortality |  | up to 29 days | 
| Hospital stay: Duration of hospital stay due to COVID-19 |  | up to 29 days | 
| Oxygen: Need of, time to first receiving and duration of oxygen |  | up to 29 days | 
| Intensive care: Need of, time to first receiving and duration of intensive care |  | up to 29 days | 
| Mechanical ventilation: Need of, time to first receiving and duration of mechanical ventilation |  | up to 29 days | 
| ECMO: Need of, time to first receiving and duration for extracorporeal membrane oxygenation |  | up to 29 days | 
| Superinfections, assessed with pathogen testing |  | up to 29 days | 
| Kidney failure |  | up to 29 days | 
| Myocardial failure |  | up to 29 days | 
| Multiple organ failure |  | up to 29 days |