Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results
BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with C...
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2020
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| author | Alvarez Manrique, Victor Daniel |
| author_browse | Alvarez Manrique, Victor Daniel |
| author_facet | Alvarez Manrique, Victor Daniel |
| author_sort | Alvarez Manrique, Victor Daniel |
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| description | BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.). |
| format | Article |
| id | oai:cris.upeu.edu.pe:20.500.15037/1056 |
| institution | UPeU |
| language | English |
| publishDate | 2020 |
| publishDateRange | 2020 |
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| spelling | oai:cris.upeu.edu.pe:20.500.15037/10562026-10-30T16:15:08ZRepurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial ResultsAlvarez Manrique, Victor DanielCoronavirus disease 2019 (COVID-19)InterimSolidarity2019-20 coronavirus outbreakSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)VirologyMedicinePolitical scienceInternal medicineLawOutbreakDiseasePoliticsInfectious disease (medical specialty)Interferon beta-1a therapeutic useCOVID-19 mortalityCOVID-19 Drug TreatmentAdenosine Monophosphate analogs & derivativesAdenosine Monophosphate therapeutic useAgedAlanine analogs & derivativesAlanine therapeutic useAntiviral Agents administration & dosageAntiviral Agents adverse effectsAntiviral Agents therapeutic useDrug Therapy, CombinationFemaleHospitalizationHumansHydroxychloroquine therapeutic useLength of StayMaleMiddle AgedRespiration, ArtificialHospital MortalityTreatment FailureKaplan-Meier EstimateIntention to Treat AnalysisLopinavir therapeutic useHealth Sciences Medicine Infectious Diseases COVID-19 Clinical Research StudiesHealth Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 ResearchLife Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology Pharmacological Receptor Mechanisms and EffectsBACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).Articlehttps://pubmed.ncbi.nlm.nih.gov/33264556https://research-information.bris.ac.uk/en/publications/98635126-3b2a-4ee8-8bcd-ed25e5fe26e110.1056/nejmoa2023184https://hdl.handle.net/20.500.15037/1056W3110466220enNew England Journal of Medicine0028-47931533-44062020-12-022026-06-13T09:44:53Z2026-06-13T09:44:53Z |
| spellingShingle | Coronavirus disease 2019 (COVID-19) Interim Solidarity 2019-20 coronavirus outbreak Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Virology Medicine Political science Internal medicine Law Outbreak Disease Politics Infectious disease (medical specialty) Interferon beta-1a therapeutic use COVID-19 mortality COVID-19 Drug Treatment Adenosine Monophosphate analogs & derivatives Adenosine Monophosphate therapeutic use Aged Alanine analogs & derivatives Alanine therapeutic use Antiviral Agents administration & dosage Antiviral Agents adverse effects Antiviral Agents therapeutic use Drug Therapy, Combination Female Hospitalization Humans Hydroxychloroquine therapeutic use Length of Stay Male Middle Aged Respiration, Artificial Hospital Mortality Treatment Failure Kaplan-Meier Estimate Intention to Treat Analysis Lopinavir therapeutic use Health Sciences Medicine Infectious Diseases COVID-19 Clinical Research Studies Health Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 Research Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology Pharmacological Receptor Mechanisms and Effects Alvarez Manrique, Victor Daniel Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results |
| title | Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results |
| title_full | Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results |
| title_fullStr | Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results |
| title_full_unstemmed | Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results |
| title_short | Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results |
| title_sort | repurposed antiviral drugs for covid 19 interim who solidarity trial results |
| topic | Coronavirus disease 2019 (COVID-19) Interim Solidarity 2019-20 coronavirus outbreak Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Virology Medicine Political science Internal medicine Law Outbreak Disease Politics Infectious disease (medical specialty) Interferon beta-1a therapeutic use COVID-19 mortality COVID-19 Drug Treatment Adenosine Monophosphate analogs & derivatives Adenosine Monophosphate therapeutic use Aged Alanine analogs & derivatives Alanine therapeutic use Antiviral Agents administration & dosage Antiviral Agents adverse effects Antiviral Agents therapeutic use Drug Therapy, Combination Female Hospitalization Humans Hydroxychloroquine therapeutic use Length of Stay Male Middle Aged Respiration, Artificial Hospital Mortality Treatment Failure Kaplan-Meier Estimate Intention to Treat Analysis Lopinavir therapeutic use Health Sciences Medicine Infectious Diseases COVID-19 Clinical Research Studies Health Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 Research Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology Pharmacological Receptor Mechanisms and Effects |
| topic_facet | Coronavirus disease 2019 (COVID-19) Interim Solidarity 2019-20 coronavirus outbreak Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Virology Medicine Political science Internal medicine Law Outbreak Disease Politics Infectious disease (medical specialty) Interferon beta-1a therapeutic use COVID-19 mortality COVID-19 Drug Treatment Adenosine Monophosphate analogs & derivatives Adenosine Monophosphate therapeutic use Aged Alanine analogs & derivatives Alanine therapeutic use Antiviral Agents administration & dosage Antiviral Agents adverse effects Antiviral Agents therapeutic use Drug Therapy, Combination Female Hospitalization Humans Hydroxychloroquine therapeutic use Length of Stay Male Middle Aged Respiration, Artificial Hospital Mortality Treatment Failure Kaplan-Meier Estimate Intention to Treat Analysis Lopinavir therapeutic use Health Sciences Medicine Infectious Diseases COVID-19 Clinical Research Studies Health Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 Research Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology Pharmacological Receptor Mechanisms and Effects |
| url | https://pubmed.ncbi.nlm.nih.gov/33264556 https://research-information.bris.ac.uk/en/publications/98635126-3b2a-4ee8-8bcd-ed25e5fe26e1 https://hdl.handle.net/20.500.15037/1056 |
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