The (Norwegian) NOR Solidarity Multicenter Trial on the Efficacy of Different Anti-viral Drugs in SARS-CoV-2 Infected Patients
Latest Information Update: 09 Apr 2022
At a glance
- Drugs Remdesivir (Primary) ; Hydroxychloroquine
- Indications SARS-CoV-2 acute respiratory disease
- Focus Therapeutic Use
- Acronyms N-ReCOVID 19; NOR-SOLIDARITY; S-ReCOVID 19
- 13 Jul 2021 Results (n=185) published in the Annals of Internal Medicine
- 15 Jan 2021 This trial has been discontinued in Sweden, according to European Clinical Trials Database record.
- 08 Jun 2020 Protocol has been amended to remove Hydroxychloroquine as a treatment group after advice from the steering committee because of lack of evidence of its effectiveness, confirmed in both internal WHO interim analyses and an external report from the RECOVERY study
Most Recent Events
Trial Overview
Purpose
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.
Primary Endpoints
In-hospital mortality
description: All cause in-hospital mortality
time_frame: 3 weeks
Other Endpoints
Occurrence and duration of mechanical ventilation
time_frame: 3 weeks
Occurrence and duration of intensive care unit (ICU) treatment
time_frame: 3 weeks
Duration of hospital admittance
time_frame: 1 month
28 Day mortality
time_frame: 3 weeks
Viral clearance as assessed by SARS-CoV-2 PCR in peripheral blood and nasopharyngeal airway speciemen
time_frame: 3 weeks
Occurrence of co-infections
time_frame: 3 weeks
Occurrence of organ dysfunction
time_frame: 3 months
Inflammatory and anti-inflammatory mediators as assessed in serum and plasma
time_frame: Throughout hospitalization
Markers of extracellular matrix remodeling
time_frame: Throughout hospitalization and 3 months after remission
Markers of endothelial activation
time_frame: Throughout hospitalization
Markers of platelet activation
time_frame: Throughout hospitalization [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| SARS-CoV-2 acute respiratory disease | treatment | - |
Subjects
- Subject Type patients
-
Number
Planned: 1218
- Sex male & female
- Age Group ≥ 18 years; adult; elderly
Patient 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
Patient 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)
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04321616 | ClinicalTrials.gov: US National Institutes of Health |
| EudraCT2020-000982-18 | European Clinical Trials Database |
| WHO-NOR-COVID19 | - |
| NOR-SOLIDARITY | - |
| 20/04950-23 | - |
| 2020201 | - |
| 118684 | - |
Trial Dates
-
Initiation Dates
Planned : 26 Mar 2020
Actual : 28 Mar 2020
-
Primary Completion Dates
Planned : 01 Aug 2020
-
End Dates
Planned : 01 Nov 2020
Substudies/Extensions
POPulation PharmacoKinetic (POPPK) study of antiviral drugs in SARS-CoV-2 infected patients participating in The Investigational NOR-SOLIDARITY study. Version 6, 28 April 2020. Primary objective: To develop novel population pharmacokinetic models for Remdesivir and Hydroxychloroquine in moderate/severe COVID-19 patients. Explorative objective: Assess viral decay, CRP/ IL-6 levels, SUSARs and Grade 3 and 4 AEs, myocardial failure/ QT-time prolongation, eGFR reduction of > 50% from baseline.
Other Details
- Design multicentre; open; parallel; prospective; randomised
- Phase of Trial Phase II/III
- Location Norway
- Focus Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| Hydroxychloroquine | Oral |
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|
| RemdesivirPrimary Drug | Intravenous | Infusion |
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.)
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.)
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.)
Results
Publications
-
Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, Kasine T, Lund-Johansen F, Hoel H, et al. Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Ann-Intern-Med 2021;.
PubMed | CrossRef Fulltext
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Andreas Barratt-Due, MD, PhD
0047 98209974
show details
andreas.barrattdue@gmail.com |
Oslo University Hospital | Norway |
| Anne Margarita Dyrhol Riise, MD, Professor | Oslo University Hospital | Norway |
| Inge Christoffer Olsen, PhD | NorCRIN |
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|
| Katerina Nezvalova-Henriksen, Pharm D, PhD | Oslo Hospital Pharmacies |
-
|
| Marius Trøseid, MD, PhD | Oslo University Hospital | Norway |
|
Paul Aukrust, MD, Professor
0047 46778374
show details
paukrust@ous-hf.no |
Oslo University Hospital | Norway |
|
Pål Aukrust, PhD
+47 46778374 paukrust@ous-hf.no
show details
|
Andreas Barratt-Due | Norway |
|
Sect. Clin. Imm. & Infect. Diseases
Sognsvannsveien 20 Oslo Postcode: 0372 Norway Telephone: +4723071916 andreas.barrattdue@gmail.com |
Oslo University Hospital | Norway |
| Trine Kåsine, MD | Oslo University Hospital | Norway |
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| Andreas Barratt-Due | Oslo | Norway |
| NorCRIN |
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|
-
|
| Oslo Hospital Pharmacies |
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|
-
|
| Oslo University Hospital |
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|
-
|
| Oslo University Hospital | oslo | Norway |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 09 Apr 2022 | Other trial event | According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified Apr 2020). Updated 09 Apr 2022 |
| 09 Apr 2022 | Other trial event | Last checked against Clinicaltrials.gov record. Updated 09 Apr 2022 |
| 13 Jul 2021 | Results | Results (n=185) published in the Annals of Internal Medicine Updated 21 Jul 2021 |
| 15 Jan 2021 | Other trial event | This trial has been discontinued in Sweden, according to European Clinical Trials Database record. Updated 15 Jan 2021 |
| 15 Jan 2021 | Other trial event | Last checked against European Clinical Trials Database record. Updated 15 Jan 2021 |
| 08 Jun 2020 | Protocol amendment | Protocol has been amended to remove Hydroxychloroquine as a treatment group after advice from the steering committee because of lack of evidence of its effectiveness, confirmed in both internal WHO interim analyses and an external report from the RECOVERY study Updated 21 Jul 2021 |
| 17 Apr 2020 | Other trial event | New source identified and integrated European Clinical Trials Database (EudraCT2020-000982-18) Updated 17 Apr 2020 |
| 10 Apr 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 15 Apr 2020 |
| 30 Mar 2020 | New trial record | New trial record Updated 30 Mar 2020 |
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
European Clinical Trials Database. Trial-Reg 2023;.
Available from: URL: https://www.clinicaltrialsregister.eu -
Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, Kasine T, Lund-Johansen F, Hoel H, et al. Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Ann-Intern-Med 2021;.
PubMed | CrossRef Fulltext
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