Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial

DOI record: { "DOI": "10.1101/2021.02.01.21250371", "URL": "http://dx.doi.org/10.1101/2021.02.01.21250371", "abstract": "<jats:title>ABSTRACT</jats:title><jats:p>The novel coronavirus pandemic (COVID–19) represents a major public health problem due to its rapid spread and its ability to generate severe pneumonia. Thus, it is essential to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo.</jats:p><jats:sec><jats:title>Material and methods</jats:title><jats:p>A double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO<jats:sub>2</jats:sub> of 65% ± 20, tachycardic (pulse rate 108±17 min-<jats:sup>1</jats:sup>) and tachypneic (32 ±10 min-<jats:sup>1</jats:sup>); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51-1.53). In the surviving participants, no significant difference was found in secondary outcomes.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>No beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19.</jats:p></jats:sec><jats:sec><jats:title>CONSORT GUIDELINES</jats:title><jats:table-wrap id=\"utbl1\" orientation=\"portrait\" position=\"float\"><jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"21250371v1_utbl1\" position=\"float\" orientation=\"portrait\" /></jats:table-wrap></jats:sec>", "accepted": { "date-parts": [ [ 2021, 2, 5 ] ] }, "author": [ { "affiliation": [], "family": "Hernandez-Cardenas", "given": "Carmen", "sequence": "first" }, { "affiliation": [], "family": "Thirion-Romero", "given": "Ireri", "sequence": "additional" }, { "affiliation": [], "family": "Rivera-Martinez", "given": "Norma E.", "sequence": "additional" }, { "affiliation": [], "family": "Meza-Meneses", "given": "Patricia", "sequence": "additional" }, { "affiliation": [], "family": "Remigio-Luna", "given": "Arantxa", "sequence": "additional" }, { "affiliation": [], "family": "Perez-Padilla", "given": "Rogelio", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 2, 5 ] ], "date-time": "2021-02-05T21:20:16Z", "timestamp": 1612560016000 }, "deposited": { "date-parts": [ [ 2021, 12, 15 ] ], "date-time": "2021-12-15T15:46:40Z", "timestamp": 1639583200000 }, "group-title": "Respiratory Medicine", "indexed": { "date-parts": [ [ 2024, 3, 1 ] ], "date-time": "2024-03-01T23:36:09Z", "timestamp": 1709336169354 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 4, "issued": { "date-parts": [ [ 2021, 2, 5 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2021.02.01.21250371", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2021, 2, 5 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2021, 2, 5 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "DOI": "10.1016/S0140-6736(20)30154-9", "doi-asserted-by": "publisher", "key": "2021020706551270000_2021.02.01.21250371v1.1" }, { "DOI": "10.1016/S0140-6736(20)30211-7", "doi-asserted-by": "crossref", "key": "2021020706551270000_2021.02.01.21250371v1.2", "unstructured": "Chen N , Zhou M , Dong X , et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020." }, { "DOI": "10.1056/NEJMoa2001191", "doi-asserted-by": "publisher", "key": "2021020706551270000_2021.02.01.21250371v1.3" }, { "DOI": "10.1038/s41586-020-2012-7", "doi-asserted-by": "publisher", "key": "2021020706551270000_2021.02.01.21250371v1.4" }, { "DOI": "10.1056/NEJMoa2001017", "doi-asserted-by": "publisher", "key": "2021020706551270000_2021.02.01.21250371v1.5" }, { "key": "2021020706551270000_2021.02.01.21250371v1.6", "unstructured": "World Health Organization. Coronavirus disease (COVID-19) Situation Report– 179. 2020; https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200717-covid-19-sitrep-179.pdf?sfvrsn=2f1599fa_2. Accessed July 18, 2020." }, { "DOI": "10.1038/s41422-020-0282-0", "doi-asserted-by": "publisher", "key": "2021020706551270000_2021.02.01.21250371v1.7" }, { "DOI": "10.1056/NEJMoa2007764", "doi-asserted-by": "publisher", "key": "2021020706551270000_2021.02.01.21250371v1.8" }, { "key": "2021020706551270000_2021.02.01.21250371v1.9", "unstructured": "Recovery Collaborative Group, Horby P , Lim WS , et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. The New England journal of medicine. 2020." }, { "key": "2021020706551270000_2021.02.01.21250371v1.10", "unstructured": "Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. 2020; https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19." }, { "key": "2021020706551270000_2021.02.01.21250371v1.11", "unstructured": "World Health Organization. WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19. 2020; https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19." }, { "key": "2021020706551270000_2021.02.01.21250371v1.12", "unstructured": "National Institutes of Health. NIH halts clinical trial of hydroxychloroquine. 2020; https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine. 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