دورية أكاديمية
Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.
| العنوان: | Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial. |
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| المؤلفون: | Schilling WHK; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Mukaka M; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Callery JJ; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Llewelyn MJ; Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton, United Kingdom.; Department of Microbiology and Infection, University Hospitals Sussex NHS Foundation Trust, Brighton, United Kingdom., Cruz CV; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Dhorda M; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Ngernseng T; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Waithira N; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Ekkapongpisit M; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Watson JA; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam., Chandna A; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia., Nelwan EJ; Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, Dr. Cipto Mangukusumo Hospital, Jakarta, Indonesia., Hamers RL; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford University Clinical Research Unit Indonesia, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Etyang A; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Beg MA; Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan., Sow S; Centre pour le Développement des Vaccins (CVD-Mali), Bamako, Mali., Yavo W; Centre de Recherche et de Lutte contre le Paludisme, Institut National de Santé Publique, Abidjan, Côte d'Ivoire., Allabi AC; Faculty of Health Sciences, Laboratory of Pharmacology and Toxicology, University of Abomey-Calavi, Cotonou, Benin., Basnyat B; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford University Clinical Research Unit Nepal, Lalitpur, Nepal., Sharma SK; B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal., Amofa-Sekyi M; Zambart, University of Zambia School of Public Health, Lusaka, Zambia., Yonga P; Fountain Health Care Hospital, Fountain Projects and Research Office (FOPRO), Eldoret, Kenya., Adler A; Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Yuentrakul P; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Cope T; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Thaipadungpanit J; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Rienpradub P; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Imwong M; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Abdad MY; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Blacksell SD; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Tarning J; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Goudjo FF; Coordination of Allada Ze Toffo Health Zone, Adjian, Benin., Dossou AD; National Public Health Laboratory, Cotonou, Benin., Konaté-Touré A; Centre de Recherche et de Lutte contre le Paludisme, Institut National de Santé Publique, Abidjan, Côte d'Ivoire., Assi SB; Institut Pierre Richet, Institut National de Santé, Publique, Bouaké, Côte d'Ivoire., Ouffoué K; Centre Hospitalier Universitaire (CHU) de Bouaké, Bouaké, Côte d'Ivoire., Nasronudin N; Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.; Universitas Airlangga Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia., Rachman BE; Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.; Universitas Airlangga Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia., Romadhon PZ; Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.; Universitas Airlangga Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia., Dewanto DD; Husada Utama Hospital, Surabaya, Indonesia., Heryana MO; Husada Utama Hospital, Surabaya, Indonesia., Novi T; Husada Utama Hospital, Surabaya, Indonesia., Pasaribu AP; Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia., Mutiara M; Murni Teguh Hospital, Medan, Medan, Indonesia., Nasution MPR; Murni Teguh Hospital, Medan, Medan, Indonesia., Khairunnisa K; Murni Teguh Hospital, Medan, Medan, Indonesia., Dalimunthe FA; Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia., Airlangga E; Bunda Thamrin Hospital, Medan, Indonesia., Fahrezzy A; Bunda Thamrin Hospital, Medan, Indonesia., Subronto Y; Department of Internal Medicine, Faculty of Medicine, Public Health And Nursing, Universitas Gadjah Mada/ Dr. Sardjito Hospital, Yogyakarta, Indonesia., Ananda NR; Dr. Sardjito Hospital, Yogyakarta, Indonesia., Rahardjani M; Oxford University Clinical Research Unit Indonesia, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Rimainar A; Oxford University Clinical Research Unit Indonesia, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Lucinde RK; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Timbwa M; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Onyango OE; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Agutu C; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Akech S; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Hamaluba M; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Kipyego J; Fountain Health Care Hospital, Fountain Projects and Research Office (FOPRO), Eldoret, Kenya., Ngachi O; Fountain Health Care Hospital, Fountain Projects and Research Office (FOPRO), Eldoret, Kenya., Haidara FC; Centre pour le Développement des Vaccins (CVD-Mali), Bamako, Mali., Traoré OY; Centre pour le Développement des Vaccins (CVD-Mali), Bamako, Mali., Diarra F; Centre pour le Développement des Vaccins (CVD-Mali), Bamako, Mali., Khanal B; B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal., Dahal P; B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal., Shrestha S; Oxford University Clinical Research Unit Nepal, Lalitpur, Nepal., Rijal S; Oxford University Clinical Research Unit Nepal, Lalitpur, Nepal., Kabore Y; Epicentre, Niamey, Niger., Adehossi E; Université Abdou Moumouni de Niamey, Faculté des Science de la Santé, Niamey, Niger., Guindo O; Epicentre, Niamey, Niger., Qamar FN; Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan., Kazi AM; Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan., Woodrow CJ; Infectious Diseases Department, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.; University of Oxford, Medical Sciences Division, John Radcliffe Hospital, Oxford, United Kingdom., Laird S; University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, United Kingdom., Cheeba M; Zambart, University of Zambia School of Public Health, Lusaka, Zambia., Ayles H; Zambart, University of Zambia School of Public Health, Lusaka, Zambia.; Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom., Cheah PY; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Taylor WRJ; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Batty EM; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Chotivanich K; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Pukrittayakamee S; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Phumratanaprapin W; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., von Seidlein L; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Dondorp A; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Day NPJ; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., White NJ; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. |
| مؤلفون مشاركون: | COPCOV Collaborative Group |
| المصدر: | PLoS medicine [PLoS Med] 2024 Sep 12; Vol. 21 (9), pp. e1004428. Date of Electronic Publication: 2024 Sep 12 (Print Publication: 2024). |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101231360 Publication Model: eCollection Cited Medium: Internet ISSN: 1549-1676 (Electronic) Linking ISSN: 15491277 NLM ISO Abbreviation: PLoS Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science, [2004]- |
| مواضيع طبية MeSH: | Hydroxychloroquine*/therapeutic use , Hydroxychloroquine*/adverse effects , Chloroquine*/therapeutic use , Chloroquine*/adverse effects , COVID-19 Drug Treatment* , COVID-19*/prevention & control , COVID-19*/epidemiology , SARS-CoV-2*, Humans ; Double-Blind Method ; Female ; Adult ; Male ; Middle Aged ; Antiviral Agents/therapeutic use ; Antiviral Agents/adverse effects ; Treatment Outcome ; Young Adult |
| مستخلص: | Background: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. Methods and Findings: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. Interpretation: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. Trial Registration: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947. Competing Interests: NJW and LvS are members of the PLOS Medicine Editorial Board. The rest of the authors have declared that no competing interests exist. (Copyright: © 2024 Schilling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT04303507 |
| المشرفين على المادة: | 4QWG6N8QKH (Hydroxychloroquine) 886U3H6UFF (Chloroquine) 0 (Antiviral Agents) |
| تواريخ الأحداث: | Date Created: 20240912 Date Completed: 20240912 Latest Revision: 20240915 |
| رمز التحديث: | 20240915 |
| مُعرف محوري في PubMed: | PMC11392261 |
| DOI: | 10.1371/journal.pmed.1004428 |
| PMID: | 39264960 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1549-1676 |
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| DOI: | 10.1371/journal.pmed.1004428 |