The Efficacy of Different Anti-viral Drugs in COVID 19 Infected Patients

Study Overview
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Brief Summary
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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.

Official Title
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The (Norwegian) NOR Solidarity Multicenter Trial on the Efficacy of Different Anti-viral Drugs in SARS-CoV-2 Infected Patients

Conditions
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SARS-CoV Infection, COVID 19, Acute Respiratory Distress Syndrome ARDS

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, 18 years and above Confirmed SARS-2-CoV-2 infection by PCR Admitted to the hospital ward or the ICU Subjects (or legally authorized representative) provides written informed consent prior to initiation of the study Exclusion Criteria: Severe co-morbidity with life expectancy <3 months according to investigators assessment (Aspartate Transaminase/ Alanine Aminotransferase) ASAT/ALAT > 5 times the upper limit of normal Acute co-morbidity within 7 days before inclusion such as myocardial infarction Known intolerance to the available study drugs Pregnancy, possible pregnancy or breast feeding Any reason why, in the opinion of the investigators, the patient should not participate Subject participates in a potentially confounding drug or device trial during the course of the study Prolonged QT interval (>450 ms)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open randomized adaptive controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine<br> | Drug: Remdesivir<br>* Remdesivir will be given intravenously 100 mg daily for the duration of the hospitalization and up to 10 days total course. A loading dose of 200 mg at inclusion will be given.<br>Other: (Standard of Care) SoC<br>* The standard of care will be supplied to all patients not receiving a drug intervention.<br>|
| Active Comparator: Remdesivir<br> | Drug: Hydroxychloroquine<br>* Hydroxychloroquine will be given orally (in the ICU in gastrointestinal tubes) with 800 mg x 2 loading dose followed by 400 mg x 2 every day for a total of 10 days.<br>Other: (Standard of Care) SoC<br>* The standard of care will be supplied to all patients not receiving a drug intervention.<br>|
| Active Comparator: Control group - SoC<br> | Drug: Hydroxychloroquine<br>* Hydroxychloroquine will be given orally (in the ICU in gastrointestinal tubes) with 800 mg x 2 loading dose followed by 400 mg x 2 every day for a total of 10 days.<br>Drug: Remdesivir<br>* Remdesivir will be given intravenously 100 mg daily for the duration of the hospitalization and up to 10 days total course. A loading dose of 200 mg at inclusion will be given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital mortality | All cause in-hospital mortality | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence and duration of mechanical ventilation |  | 3 weeks | 
| Occurrence and duration of intensive care unit (ICU) treatment |  | 3 weeks | 
| Duration of hospital admittance |  | 1 month | 
| 28 Day mortality |  | 3 weeks | 
| Viral clearance as assessed by SARS-CoV-2 PCR in peripheral blood and nasopharyngeal airway speciemen |  | 3 weeks | 
| Occurrence of co-infections |  | 3 weeks | 
| Occurrence of organ dysfunction |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect of drugs, Adverse effects of drugs, SARS-CoV clearance, Duration of artificial ventilation, Duration of intensive care stay, Duration of hospital stay