{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:18:01Z","timestamp":1773289081602,"version":"3.50.1"},"reference-count":0,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-016204"],"award-info":[{"award-number":["INV-016204"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>\nObjectives<\/jats:title>\nPrimary Objective<\/jats:p>\n\u2022 To test the efficacy of Hydroxychloroquine (HCQ) (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection<\/jats:p>\nSecondary objectives<\/jats:p>\n\u2022 To determine the safety and tolerability of HCQ as SARS-CoV-2 Post-exposure Prophylaxis (PEP) in adults<\/jats:p>\n\u2022 To test the efficacy of HCQ (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection 2 weeks after completing therapy, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection<\/jats:p>\n\u2022 To test the efficacy of HCQ to shorten the duration of SARS-CoV-2 shedding among those with SARS-CoV-2 infection in the HCQ PEP group<\/jats:p>\n\u2022 To test the efficacy of HCQ to prevent incident COVID-19<\/jats:p>\n<\/jats:sec>\nTrial design<\/jats:title>\nThis is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of HCQ PEP for the prevention of SARS-CoV-2 infection in adults exposed to the virus.<\/jats:p>\n<\/jats:sec>\nParticipants<\/jats:title>\nThis study will enroll up to 2000 asymptomatic adults 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. This multisite trial will be conducted at seven sites in Seattle (UW), Los Angeles (UCLA), New Orleans (Tulane), Baltimore (UMB), New York City (NYU), Syracuse (SUNY-Upstate), and Boston (BMC).<\/jats:p>\nInclusion criteria<\/jats:italic><\/jats:bold><\/jats:p>\nParticipants are eligible to be included in the study only if all of the following criteria apply:\nMen or women 18 to 80 years of age inclusive, at the time of signing the informed consent<\/jats:p><\/jats:list-item>Willing and able to provide informed consent<\/jats:p><\/jats:list-item>Had a close contact of a person (index) with known PCR-confirmed SARS-CoV-2 infection or index who is currently being assessed for COVID-19<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>\nClose contact is defined as:\nHousehold contact (i.e., residing with the index case in the 14 days prior to index diagnosis or prolonged exposure within a residence\/vehicle\/enclosed space without maintaining social distance)<\/jats:p><\/jats:list-item>Medical staff, first responders, or other care persons who cared for the index case without personal protection (mask and gloves)<\/jats:p><\/jats:list-item><\/jats:list>Less than 4 days since last exposure (close contact with a person with SARS-CoV-2 infection) to the index case<\/jats:p><\/jats:list-item>Access to device and internet for Telehealth visits<\/jats:p><\/jats:list-item>Not planning to take HCQ in addition to the study medication<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>\nExclusion criteria<\/jats:italic><\/jats:bold><\/jats:p>\nParticipants are excluded from the study if any of the following criteria apply:\nKnown hypersensitivity to HCQ or other 4-aminoquinoline compounds<\/jats:p><\/jats:list-item>Currently hospitalized<\/jats:p><\/jats:list-item>Symptomatic with subjective fever, cough, or shortness of breath<\/jats:p><\/jats:list-item>Current medications exclude concomitant use of HCQ<\/jats:p><\/jats:list-item>Concomitant use of other anti-malarial treatment or chemoprophylaxis, including chloroquine, mefloquine, artemether, or lumefantrine.<\/jats:p><\/jats:list-item>History of retinopathy of any etiology<\/jats:p><\/jats:list-item>Psoriasis<\/jats:p><\/jats:list-item>Porphyria<\/jats:p><\/jats:list-item>Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes <1500) or thrombocytopenia (<100 K)<\/jats:p><\/jats:list-item>Concomitant use of digoxin, cyclosporin, cimetidine, amiodarone, or tamoxifen<\/jats:p><\/jats:list-item>Known moderate or severe liver disease<\/jats:p><\/jats:list-item>Known long QT syndrome<\/jats:p><\/jats:list-item>Severe renal impairment<\/jats:p><\/jats:list-item>Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study drugs or planned use during the study period<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>\n<\/jats:sec>\nIntervention and comparator<\/jats:title>\nHouseholds will be randomized 1:1 (at the level of household), with close contact participants receiving one of the following therapies:<\/jats:p>\n\u2022HCQ 400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days<\/jats:p>\n\u2022Placebo-like control (ascorbic acid) 500 mg orally daily for 3 days then 250 mg orally daily for 11 days<\/jats:p>\n<\/jats:sec>\nMain outcomes<\/jats:title>\nThe primary outcome of the study is the incidence of SARS-CoV-2 infection through day 14 among participants who are SARS-CoV-2 negative at baseline by randomization group.<\/jats:p>\n<\/jats:sec>\nRandomisation<\/jats:title>\nParticipants will be randomized in a 1:1 ratio to HCQ or ascorbic acid at the level of the household (all eligible participants in 1 household will receive the same intervention). The randomization code and resulting allocation list will be generated and maintained by the Study Statistician. The list will be blocked and stratified by site and contact type (household versus healthcare worker).<\/jats:p>\n<\/jats:sec>\nBlinding (masking)<\/jats:title>\nThis is a blinded study.<\/jats:p>\nHCQ and ascorbic acid will appear similar, and taste will be partially masked as HCQ can be bitter and ascorbic acid will be sour.<\/jats:p>\nThe participants will be blinded to their randomization group once assigned. Study team members, apart from the Study Pharmacist and the unblinded statistical staff, will be blinded. Laboratory staff are blinded to the group allocation.<\/jats:p>\n<\/jats:sec>\nNumbers to be randomised (sample size)<\/jats:title>\nThe sample size for the study is N<\/jats:italic>=2 000 participants randomized 1:1 to either HCZ (n<\/jats:italic>=1 000) and ascorbic acid (n<\/jats:italic>=1 000).<\/jats:p>\n<\/jats:sec>\nTrial status<\/jats:title>\nProtocol version: 1.2<\/jats:p>\n05 April 2020<\/jats:p>\nRecruitment is ongoing, started March 31 and anticipated end date is September 30, 2020.<\/jats:p>\n<\/jats:sec>\nTrial registration<\/jats:title>\nClinicalTrials.gov, Protocol Registry Number:<\/jats:bold> NCT04328961<\/jats:p>\nDate of registration: April 1, 2020, retrospectively registered<\/jats:p>\n<\/jats:sec>\nFull protocol<\/jats:title>\nThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13063-020-04446-4","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T15:05:01Z","timestamp":1591196701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Efficacy of hydroxychloroquine for post-exposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults exposed to coronavirus disease (COVID-19): a structured summary of a study protocol for a randomised controlled trial"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1793-6003","authenticated-orcid":false,"given":"Ruanne V.","family":"Barnabas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bershteyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Scott","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Wener","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connie","family":"Celum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Wald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wesche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared M.","family":"Baeten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Hydroxychloroquine COVID-19 PEP Study Team","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,3]]},"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04446-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-020-04446-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04446-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T02:14:42Z","timestamp":1622686482000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-020-04446-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,3]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4446"],"URL":"https:\/\/doi.org\/10.1186\/s13063-020-04446-4","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,3]]},"assertion":[{"value":"29 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"I certify that this trial has received ethical approval from the appropriate ethical committee as described above. The study will be conducted according to Good Clinical Practice, the Belmont Report, and the Declaration of Helsinki. The principles of informed consent in the current edition of the Declaration of Helsinki will be implemented in each clinical study before any protocol-specified procedures or interventions are carried out. The consent form will describe the purpose of the study, the procedures to be followed, and the risks and benefits of participation. A copy of the consent form will be given to the participant, and this fact will be documented in the participant\u2019s record.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AB reports personal fees from Gates Ventures. CC reports personal fees from Gilead Sciences and Merck, outside the submitted work. JMB reports personal fees from Gilead Sciences, Merck, and Janssen, outside the submitted work. HC reports grants from Sanofi-Pasteur, Ellume, Cepheid, and Genentech; and personal fees from GSK and Merck, outside the submitted work. All other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"475"}}