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

Sponsor

Oslo University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT04321616

Collaborator

(none)

700

Enrollment

Location

Arms

7.2

Anticipated Duration (Months)

97.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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	Intervention/Treatment	Phase
SARS-CoV Infection COVID 19 Acute Respiratory Distress Syndrome ARDS	Drug: Hydroxychloroquine Drug: Remdesivir Other: (Standard of Care) SoC	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

An open randomized adaptive controlled trialAn open randomized adaptive controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 28, 2020

Anticipated Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Hydroxychloroquine	Drug: Remdesivir 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. Other: (Standard of Care) SoC The standard of care will be supplied to all patients not receiving a drug intervention.
Active Comparator: Remdesivir	Drug: Hydroxychloroquine 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. Other: (Standard of Care) SoC The standard of care will be supplied to all patients not receiving a drug intervention.
Active Comparator: Control group - SoC	Drug: Hydroxychloroquine 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. Drug: Remdesivir 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.

Arm

Intervention/Treatment

Active Comparator: Hydroxychloroquine

Drug: Remdesivir

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.

Other: (Standard of Care) SoC

The standard of care will be supplied to all patients not receiving a drug intervention.

Active Comparator: Remdesivir

Drug: Hydroxychloroquine

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.

Other: (Standard of Care) SoC

The standard of care will be supplied to all patients not receiving a drug intervention.

Active Comparator: Control group - SoC

Drug: Hydroxychloroquine

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.

Drug: Remdesivir

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.

Outcome Measures

Primary Outcome Measures

In-hospital mortality [3 weeks]
All cause in-hospital mortality

Secondary Outcome Measures

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]

Other Outcome Measures

Inflammatory and anti-inflammatory mediators as assessed in serum and plasma [Throughout hospitalization]
Markers of extracellular matrix remodeling [Throughout hospitalization and 3 months after remission]
Markers of endothelial activation [Throughout hospitalization]
Markers of platelet activation [Throughout hospitalization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Andreas Barratt-Due	Oslo		Norway	0756

Sponsors and Collaborators

Oslo University Hospital

Investigators

Study Chair: Paul Aukrust, MD, Professor, Oslo University Hospital
Principal Investigator: Andreas Barratt-Due, MD, PhD, Oslo University Hospital
Principal Investigator: Trine Kåsine, MD, Oslo University Hospital
Principal Investigator: Katerina Nezvalova-Henriksen, Pharm D, PhD, Oslo Hospital Pharmacies
Principal Investigator: Anne Margarita Dyrhol Riise, MD, Professor, Oslo University Hospital
Principal Investigator: Marius Trøseid, MD, PhD, Oslo University Hospital
Principal Investigator: Inge Christoffer Olsen, PhD, NorCRIN