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Evaluation of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 Patients: Results from the NOR-Solidarity Randomised Trial

33 Pages Posted: 11 Feb 2021

See all articles by Andreas Barratt-Due

Andreas Barratt-Due

University of Oslo - Division of Emergencies and Critical Care

Inge Christoffer Olsen

University of Oslo - Oslo University Hospital

Katerina Nezvalova Henriksen

University of Oslo - Oslo University Hospital

Trine Kåsine

University of Oslo - Division of Emergencies and Critical Care

Fridtjof Lund-Johansen

University of Oslo - Department of Immunology

Hedda Hoel

University of Oslo - Institute of Clinical Medicine

Aleksander Rygh Holten

University of Oslo - Institute of Clinical Medicine

Anders Tveita

Vestre Viken Hospital Trust; University of Oslo - KG Jebsen Centre for B Cell Malignancies

Alexander Mathiessen

Diakonhjemmet Hospital

Mette Haugli

Sørlandet Hospital

Ragnhild Eiken

Innlandet Hospital

Anders Benjamin Kildal

University Hospital North Norway

Åse Berg

Stavanger University Hospital

Asgeir Johannessen

University of Oslo - Institute of Clinical Medicine

Lars Heggelund

Vestre Viken Hospital Trust

Tuva Børresdatter Dahl

University of Oslo - Division of Emergencies and Critical Care

Karoline Hansen Skåra

University of Oslo - Oslo University Hospital

Pawel Mielnik

Førde Central Hospital - Department for Neurology, Rheumatology and Physical Medicine

Lan Ai Kieu Le

Haugesund Hospital

Lars Thoresen

Vestre Viken Hospital Trust

Gernot Ernst

Vestre Viken Hospital Trust

Dag Arne Lihaug Hoff

Møre & Romsdal Hospital Trust - Ålesund Hospital - Department of Medicine

Hilde Skudal

Telemark Hospital Trust

Bård Reiakvam Kittang

Haraldsplass Deaconess Hospital

Roy Bjørkholt Olsen

Sørlandet Hospital

Birgitte Tholin

Møre & Romsdal Hospital Trust - Molde Hospital - 8Department of Internal Medicine

Carl Magnus Ystrøm

Innlandet Hospital Trust

Nina Vibeche Skei

Høgskolen i Nord-Trøndelag

Trung Tran

University of Oslo - Department of Immunology

Susanne Dudman

University of Oslo - Institute of Clinical Medicine

Jan Terje Andersen

University of Oslo - Institute of Clinical Medicine

Raisa Hannula

Trondheim University Hospital

Olav Dalgard

University of Oslo - Institute of Clinical Medicine

Ane-Kristine Finbråten

Lovisenberg Diaconal Hospital

Kristian Tonby

University of Oslo - Institute of Clinical Medicine

Bjørn Blomberg

University of Bergen - Department of Clinical Science

Saad Aballi

Østfold Hospital Kalnes - Department of Infectious Diseases

Cathrine Fladeby

University of Oslo - Oslo University Hospital

Anne Steffensen

University of Oslo - Institute of Clinical Medicine

Fredrik Müller

University of Oslo - Institute of Clinical Medicine

Anne Ma Dyrhol-Riise

University of Oslo - Institute of Clinical Medicine

Marius Trøseid

University of Oslo - Institute of Clinical Medicine

Pål Aukrust

University of Oslo - Institute of Clinical Medicine

More...

Abstract

Background: There is an urgent need for new treatment modalities in COVID-19 patients. Recently, the WHO Solidarity trial showed no effects of remdesivir or hydroxychloroquine (HCQ) on mortality. However, the antiviral effects of these drugs and the possible relation to clinical characteristics at admission is not known.

Methods: NOR-Solidarity is an independent add-on study to the WHO Solidarity trial, including biobanking, and a clinical three-month follow-up. Eligible patients were adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection. Patients were randomly assigned to receive remdesivir, HCQ or standard of care (SoC). In-hospital mortality, admission to intensive care unit and initiation of mechanical ventilation were primary and secondary clinical endpoints shared with WHO Solidarity. Secondary endpoints were impact of remdesivir or HCQ on SARS-CoV-2 clearance in the oropharynx, as well as their effects on systemic inflammation and the degree of respiratory failure (ClinicalTrials.gov: NCT04321616).

Findings: Between March 28 and October 4, 185 patients from 23 hospitals in Norway were randomized and 181 included in the full analysis set: remdesivir (n=42), HCQ (n=52) and SoC (n=87). No significant differences in mortality during hospitalisation, ICU admission or occurrence of mechanical ventilation between the treatment groups and SoC were observed. There was a marked decrease in SARS-CoV-2 load in oropharynx during the first week with similar decrease and 10-day levels between remdesivir, HCQ and their respective SoC. Remdesivir and HCQ did not exert any effect on the degree of respiratory failure or on inflammatory parameters in peripheral blood. Notably, the lack of anti-viral effect was not associated with symptom duration, level of viral load or presence of antibodies against SARS-CoV-2 at hospital admittance.

Interpretation: We found no effect on viral clearance by either remdesivir or HCQ in hospitalised COVID-19 patients.

Trial Registration: (ClinicalTrials.gov: NCT04321616)

Funding: National Clinical Therapy Research in the Specialist Health Services, Norway.

Declaration of Interests: All authors declare no competing interest.

Ethics Approval Statement: The trial protocol was approved by the Regional Ethic Committee (118684) and by the Norwegian Medicines Agency (20/04950-23) and was overseen by an independent data and safety monitoring board.

Suggested Citation

Barratt-Due, Andreas and Olsen, Inge Christoffer and Henriksen, Katerina Nezvalova and Kåsine, Trine and Lund-Johansen, Fridtjof and Hoel, Hedda and Holten, Aleksander Rygh and Tveita, Anders and Mathiessen, Alexander and Haugli, Mette and Eiken, Ragnhild and Kildal, Anders Benjamin and Berg, Åse and Johannessen, Asgeir and Heggelund, Lars and Dahl, Tuva Børresdatter and Skåra, Karoline Hansen and Mielnik, Pawel and Le, Lan Ai Kieu and Thoresen, Lars and Ernst, Gernot and Hoff, Dag Arne Lihaug and Skudal, Hilde and Kittang, Bård Reiakvam and Olsen, Roy Bjørkholt and Tholin, Birgitte and Ystrøm, Carl Magnus and Skei, Nina Vibeche and Tran, Trung and Dudman, Susanne and Andersen, Jan Terje and Hannula, Raisa and Dalgard, Olav and Finbråten, Ane-Kristine and Tonby, Kristian and Blomberg, Bjørn and Aballi, Saad and Fladeby, Cathrine and Steffensen, Anne and Müller, Fredrik and Dyrhol-Riise, Anne Ma and Trøseid, Marius and Aukrust, Pål, Evaluation of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 Patients: Results from the NOR-Solidarity Randomised Trial. Available at SSRN: https://ssrn.com/abstract=3774182 or http://dx.doi.org/10.2139/ssrn.3774182

Andreas Barratt-Due (Contact Author)

University of Oslo - Division of Emergencies and Critical Care ( email )

N-0027 Oslo
Norway
+47 98209974 (Phone)

Inge Christoffer Olsen

University of Oslo - Oslo University Hospital ( email )

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Katerina Nezvalova Henriksen

University of Oslo - Oslo University Hospital ( email )

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Trine Kåsine

University of Oslo - Division of Emergencies and Critical Care ( email )

P. B. 4950 Nydalen
0424 Oslo
Norway

Fridtjof Lund-Johansen

University of Oslo - Department of Immunology ( email )

P. B. 4950 Nydalen
0424 Oslo
Norway

Hedda Hoel

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Aleksander Rygh Holten

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Anders Tveita

Vestre Viken Hospital Trust ( email )

Drammen
Norway

University of Oslo - KG Jebsen Centre for B Cell Malignancies ( email )

Norway

Alexander Mathiessen

Diakonhjemmet Hospital ( email )

Oslo
Norway

Mette Haugli

Sørlandet Hospital ( email )

Kristiansand
Norway

Ragnhild Eiken

Innlandet Hospital ( email )

Lillehammer
Norway

Anders Benjamin Kildal

University Hospital North Norway ( email )

Tromsø
Norway

Åse Berg

Stavanger University Hospital ( email )

Armauer Hansens vei 20
Stavanger, 4011
Norway

Asgeir Johannessen

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Lars Heggelund

Vestre Viken Hospital Trust

Drammen
Norway

Tuva Børresdatter Dahl

University of Oslo - Division of Emergencies and Critical Care ( email )

P. B. 4950 Nydalen
0424 Oslo
Norway

Karoline Hansen Skåra

University of Oslo - Oslo University Hospital ( email )

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Pawel Mielnik

Førde Central Hospital - Department for Neurology, Rheumatology and Physical Medicine ( email )

6812 Førde
Norway

Lan Ai Kieu Le

Haugesund Hospital ( email )

Haugesund
Norway

Lars Thoresen

Vestre Viken Hospital Trust ( email )

Drammen
Norway

Gernot Ernst

Vestre Viken Hospital Trust ( email )

Drammen
Norway

Dag Arne Lihaug Hoff

Møre & Romsdal Hospital Trust - Ålesund Hospital - Department of Medicine ( email )

6026 Ålesund
Norway

Hilde Skudal

Telemark Hospital Trust ( email )

Skien
Norway

Bård Reiakvam Kittang

Haraldsplass Deaconess Hospital ( email )

Bergen
Norway

Roy Bjørkholt Olsen

Sørlandet Hospital ( email )

Kristiansand
Norway

Birgitte Tholin

Møre & Romsdal Hospital Trust - Molde Hospital - 8Department of Internal Medicine ( email )

6412 Molde
Norway

Carl Magnus Ystrøm

Innlandet Hospital Trust ( email )

Lillehammer
Norway

Nina Vibeche Skei

Høgskolen i Nord-Trøndelag ( email )

Steinkjer
Norway

Trung Tran

University of Oslo - Department of Immunology

P. B. 4950 Nydalen
0424 Oslo
Norway

Susanne Dudman

University of Oslo - Institute of Clinical Medicine

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Jan Terje Andersen

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Raisa Hannula

Trondheim University Hospital ( email )

Norway

Olav Dalgard

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Ane-Kristine Finbråten

Lovisenberg Diaconal Hospital ( email )

Oslo
Norway

Kristian Tonby

University of Oslo - Institute of Clinical Medicine

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Bjørn Blomberg

University of Bergen - Department of Clinical Science ( email )

Norway

Saad Aballi

Østfold Hospital Kalnes - Department of Infectious Diseases ( email )

1714 Grålum
Norway

Cathrine Fladeby

University of Oslo - Oslo University Hospital ( email )

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Anne Steffensen

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Fredrik Müller

University of Oslo - Institute of Clinical Medicine

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

Anne Ma Dyrhol-Riise

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Marius Trøseid

University of Oslo - Institute of Clinical Medicine ( email )

Oslo
Norway

Pål Aukrust

University of Oslo - Institute of Clinical Medicine

Kirkeveien 166
Building 2H
Oslo, N-0450
Norway

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