Evaluation of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 Patients: Results from the NOR-Solidarity Randomised Trial
| Autor: | Tuva B. Dahl, Hilde Skudal, Ane-Kristine Finbråten, Skåra Kh, Le Lak, Kristian Tonby, Cathrine Fladeby, Bård Reiakvam Kittang, Raisa Hannula, Andreas Barratt-Due, Fridtjof Lund-Johansen, Alexander Mathiessen, Anne Margarita Dyrhol-Riise, Bjørn Blomberg, Asgeir Johannessen, Carl Magnus Ystrøm, Lars Thoresen, Katerina Nezvalova Henriksen, Hedda Hoel, Mette Haugli, Pawel Mielnik, Saad Aballi, Hoff Dal, Gernot Ernst, Birgitte Tholin, Åse Berg, Marius Trøseid, Ragnhild Eiken, Susanne Gjeruldsen Dudman, Jan Terje Andersen, Olav Dalgard, Trine Kåsine, Lars Heggelund, Steffensen A, Müller F, Anders Benjamin Kildal, Skei Nv, Roy Bjørkholt Olsen, P. Aukrust, Inge C. Olsen, Tran T, Aleksander Rygh Holten, Anders Aune Tveita |
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| Rok vydání: | 2021 |
| Předmět: |
Mechanical ventilation
medicine.medical_specialty Coronavirus disease 2019 (COVID-19) business.industry medicine.medical_treatment Hydroxychloroquine Intensive care unit law.invention Treatment and control groups Respiratory failure law Internal medicine medicine Clinical endpoint business Viral load medicine.drug |
| Zdroj: | SSRN Electronic Journal. |
| ISSN: | 1556-5068 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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