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

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID 19; SARS-CoV Infection; Acute Respiratory Distress Syndrome ARDS
• Intervention / Treatment: Drug: Remdesivir; Other: (Standard of Care) SoC; Drug: Hydroxychloroquine

• Study Type: Interventional
• Enrollment (Anticipated): 700
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0756
    • Recruiting
    • Andreas Barratt-Due
    • Contact: ANDREAS BARRATT-DUE, PhD; Phone Number: +47 98209974; Email: andreas.barrattdue@gmail.com
    • Contact: Pål Aukrust, PhD; Phone Number: +47 46778374; Email: paukrust@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients, 18 years and above
2. Confirmed SARS-2-CoV-2 infection by PCR
3. Admitted to the hospital ward or the ICU
4. Subjects (or legally authorized representative) provides written informed consent prior to initiation of the study

Exclusion Criteria:

1. Severe co-morbidity with life expectancy <3 months according to investigators assessment
2. (Aspartate Transaminase/ Alanine Aminotransferase) ASAT/ALAT > 5 times the upper limit of normal
3. Acute co-morbidity within 7 days before inclusion such as myocardial infarction
4. Known intolerance to the available study drugs
5. Pregnancy, possible pregnancy or breast feeding
6. Any reason why, in the opinion of the investigators, the patient should not participate
7. Subject participates in a potentially confounding drug or device trial during the course of the study
8. Prolonged QT interval (>450 ms)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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	Other: (Standard of Care) SoC; The standard of care will be supplied to all patients not receiving a drug intervention.; 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.
Active Comparator: Control group - SoC	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.; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: 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: Inge Christoffer Olsen, PhD, NorCRIN

Publications and helpful links

General Publications

• Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.
• Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, Kasine T, Lund-Johansen F, Hoel H, Holten AR, Tveita A, Mathiessen A, Haugli M, Eiken R, Kildal AB, Berg A, Johannessen A, Heggelund L, Dahl TB, Skara KH, Mielnik P, Le LAK, Thoresen L, Ernst G, Hoff DAL, Skudal H, Kittang BR, Olsen RB, Tholin B, Ystrom CM, Skei NV, Tran T, Dudman S, Andersen JT, Hannula R, Dalgard O, Finbraten AK, Tonby K, Blomberg B, Aballi S, Fladeby C, Steffensen A, Muller F, Dyrhol-Riise AM, Troseid M, Aukrust P; NOR-Solidarity trial. Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Ann Intern Med. 2021 Sep;174(9):1261-1269. doi: 10.7326/M21-0653. Epub 2021 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2020
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2020
• Last Update Submitted That Met QC Criteria: April 10, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Effect of drugs; Adverse effects of drugs; SARS-CoV clearance; Duration of artificial ventilation; Duration of intensive care stay; Duration of hospital stay
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine; Remdesivir
• Other Study ID Numbers: 118684

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All patients included in this study will automatically be included in the WHO COVID 19 protocol
• IPD Sharing Time Frame: The study will end according the requirements to WHO
• IPD Sharing Access Criteria: WHO COVID 19 investigators
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No