Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials
Hwanhee Hong, Anne Friedland, Mengyi Hu, Kevin J Anstrom, Susan Halabi, John E Mckinnon, Ravi Amaravadi, Jorge Rojas-Serrano, Benjamin S Abella, Angélica Margarita Portillo-Vázquez, Christopher W Woods, Adrian F Hernandez, David R Boulware, Susanna Naggie, Radha Rajasingham
BMJ Open, doi:10.1136/bmjopen-2022-065305
Objective We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a metaanalysis of randomised controlled trials (RCTs). Data sources PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. Study selection Ten RCTs were identified (n=5079 participants). Data extraction and synthesis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and metaanalysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written. Main outcomes The primary efficacy outcome was PCRconfirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection. Results Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73). Conclusions and relevance Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as preexposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events. PROSPERO registration number CRD42021285093.
Competing interests All authors except BSA reported no financial relationship with commercial interest. BSA has received NIH funds for COVID-19-related research and holds equity in VOC Health, a start-up company that is developing novel COVID-19 testing. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not required. Ethics approval Ethics approval was not required because this study used publicly available aggregate data that were not involved with patients' information or prospective data collection. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or..
References
Abella, Jolkovsky, Biney, Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-Cov-2 prophylaxis among health care workers: a randomized clinical trial, JAMA Intern Med,
doi:10.1001/jamainternmed.2020.6319Developent, Rstan: the R interface to Stan. R Package Version
Ferreira, Ludes, Diemunsch, Bayesian predictive probabilities: a good way to monitor clinical trials, Br J Anaesth,
doi:10.1016/j.bja.2020.08.062García-Albéniz, Amo, Polo, Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19, Eur J Epidemiol,
doi:10.1007/s10654-022-00891-4Grau-Pujol, Camprubí-Ferrer, Marti-Soler, Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial, Trials,
doi:10.1186/s13063-021-05758-9Halabi, Zhou, He, Landscape of Coronavirus disease 2019 clinical trials: new frontiers and challenges, Clin Trials,
doi:10.1177/17407745221105106Hong, Carlin, Shamliyan, Comparing Bayesian and Frequentist approaches for multiple outcome mixed treatment comparisons, Med Decis Making,
doi:10.1177/0272989X13481110Hong, Chu, Zhang, A Bayesian missing data framework for generalized multiple outcome mixed treatment comparisons, Res Syn Meth,
doi:10.1002/jrsm.1153Hong, Wang, Rosner, Meta-analysis of rare adverse events in randomized clinical trials: Bayesian and Frequentist methods, Clin Trials,
doi:10.1177/1740774520969136Hutton, Salanti, Caldwell, The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations, Ann Intern Med,
doi:10.7326/M14-2385Infante, Ricordi, Hydroxychloroquine to prevent SARS-Cov-2 infection among Healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial, Expert Rev Anti Infect Ther,
doi:10.1186/s13104-023-06281-7Kalil, Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during Pandemics, JAMA,
doi:10.1001/jama.2020.4742Lofgren, Nicol, Bangdiwala, Safety of hydroxychloroquine among outpatient clinical trial participants for covid-19, Open Forum Infectious Diseases,
doi:10.1093/ofid/ofaa500Mccreary, Pogue, Pharmacists. Coronavirus disease 2019 treatment: A review of early and emerging options, Open Forum Infect Dis,
doi:10.1093/ofid/ofaa105Mckinnon, Wang, Zervos, Safety and tolerability of hydroxychloroquine in health care workers and first responders for the prevention of COVID-19: WHIP COVID-19 study, Int J Infect Dis,
doi:10.1016/j.ijid.2021.12.343Nabaggala, Nair, Gacic-Dobo, The global inequity in COVID-19 vaccination coverage among health and care workers, Int J Equity Health,
doi:10.1186/s12939-022-01750-0Naggie, Milstone, Castro, Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare worker exposure response and outcomes of hydroxychloroquine (HERO-HCQ), Int J Infect Dis,
doi:10.1016/j.ijid.2023.01.019Polo, García-Albéniz, Terán, Daily tenofovir disoproxil fumarate/Emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in Healthcare workers, Clin Microbiol Infect,
doi:10.1016/j.cmi.2022.07.006Puhan, Schünemann, Murad, A GRADE working group approach for rating the quality of treatment effect estimates from network meta-analysis, BMJ,
doi:10.1136/bmj.g5630Rajasingham, Bangdiwala, Nicol, Hydroxychloroquine as pre-exposure prophylaxis for Coronavirus disease 2019 (COVID-19) in Healthcare workers: A randomized trial, Clin Infect Dis,
doi:10.1093/cid/ciaa1571Rojas-Serrano, Portillo-Vásquez, Thirion-Romero, Hydroxychloroquine for prophylaxis of COVID-19 in health workers: a randomized clinical trial, PLoS One,
doi:10.1371/journal.pone.0261980Seet, Quek, Ooi, Positive impact of oral hydroxychloroquine and Povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial, Int J Infect Dis,
doi:10.1016/j.ijid.2021.04.035Skipper, Pastick, Engen, Hydroxychloroquine in Nonhospitalized adults with early COVID-19: A randomized trial, Ann Intern Med,
doi:10.7326/M20-4207Sterne, Savović, Page, Rob 2: a revised tool for assessing risk of bias in randomised trials, BMJ,
doi:10.1136/bmj.l4898Syed, Hassan, Arif, Pre-exposure prophylaxis with various doses of hydroxychloroquine among Healthcare personnel on June 18, 2023 by guest, Cureus,
doi:10.7759/cureus.20572The, Group, RECOVERY collaborative group, effect of hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2022926Vijayaraghavan, Jha, Rajbhandari, Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratoryconfirmed COVID-19 infections among Healthcare workers: a Multicentre, parallel-group randomised controlled trial from India, BMJ Open,
doi:10.1136/bmjopen-2021-059540Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel Coronavirus (2019-nCoV) in vitro, Cell Res,
doi:10.1038/s41422-020-0282-0Watanabe, Opper, Asymptotic equivalence of Bayes cross validation and widely applicable information criterion in singular learning theory, J Mach Learn Res
{ 'indexed': {'date-parts': [[2023, 6, 17]], 'date-time': '2023-06-17T04:33:04Z', 'timestamp': 1686976384834},
'reference-count': 38,
'publisher': 'BMJ',
'issue': '6',
'license': [ { 'start': { 'date-parts': [[2023, 6, 16]],
'date-time': '2023-06-16T00:00:00Z',
'timestamp': 1686873600000},
'content-version': 'unspecified',
'delay-in-days': 15,
'URL': 'http://creativecommons.org/licenses/by-nc/4.0/'}],
'funder': [ { 'DOI': '10.13039/100006093',
'name': 'Patient Centered Outcomes Research Institute',
'doi-asserted-by': 'crossref',
'award': ['COVID-19-2020-001']}],
'content-domain': {'domain': ['bmj.com'], 'crossmark-restriction': True},
'published-print': {'date-parts': [[2023, 6]]},
'abstract': '<jats:sec><jats:title>Objective</jats:title><jats:p>We studied the safety and efficacy of '
'hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers '
'(HCWs), using a meta-analysis of randomised controlled trials '
'(RCTs).</jats:p></jats:sec><jats:sec><jats:title>Data sources</jats:title><jats:p>PubMed and '
'EMBASE databases were searched to identify randomised trials studying '
'HCQ.</jats:p></jats:sec><jats:sec><jats:title>Study selection</jats:title><jats:p>Ten RCTs '
'were identified (n=5079 participants).</jats:p></jats:sec><jats:sec><jats:title>Data '
'extraction and synthesis</jats:title><jats:p>The Preferred Reporting Items for Systematic '
'Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis '
'between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis '
'plan was written.</jats:p></jats:sec><jats:sec><jats:title>Main '
'outcomes</jats:title><jats:p>The primary efficacy outcome was PCR-confirmed SARS-CoV-2 '
'infection and the primary safety outcome was incidence of adverse events. The secondary '
'outcome included clinically suspected SARS-CoV-2 '
'infection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Compared with '
'placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 '
'infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected '
'SARS-CoV-2 infection (OR 0.78, 95%\u2009CI: 0.57, 1.10), but significant difference in '
'adverse events (OR 1.35, 95%\u2009CI: 1.03, '
'1.73).</jats:p></jats:sec><jats:sec><jats:title>Conclusions and '
'relevance</jats:title><jats:p>Our meta-analysis of 10 RCTs investigating the safety and '
'efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ '
'does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 '
'infection, while HCQ significantly increases adverse '
'events.</jats:p></jats:sec><jats:sec><jats:title>PROSPERO registration '
'number</jats:title><jats:p>CRD42021285093.</jats:p></jats:sec>',
'DOI': '10.1136/bmjopen-2022-065305',
'type': 'journal-article',
'created': {'date-parts': [[2023, 6, 16]], 'date-time': '2023-06-16T17:33:56Z', 'timestamp': 1686936836000},
'page': 'e065305',
'update-policy': 'http://dx.doi.org/10.1136/crossmarkpolicy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare '
'workers: a meta-analysis of randomised clinical trials',
'prefix': '10.1136',
'volume': '13',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-3736-6327',
'authenticated-orcid': False,
'given': 'Hwanhee',
'family': 'Hong',
'sequence': 'first',
'affiliation': []},
{'given': 'Anne', 'family': 'Friedland', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mengyi', 'family': 'Hu', 'sequence': 'additional', 'affiliation': []},
{'given': 'Kevin J', 'family': 'Anstrom', 'sequence': 'additional', 'affiliation': []},
{'given': 'Susan', 'family': 'Halabi', 'sequence': 'additional', 'affiliation': []},
{'given': 'John E', 'family': 'McKinnon', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-5768-2474',
'authenticated-orcid': False,
'given': 'Ravi',
'family': 'Amaravadi',
'sequence': 'additional',
'affiliation': []},
{'given': 'Jorge', 'family': 'Rojas-Serrano', 'sequence': 'additional', 'affiliation': []},
{'given': 'Benjamin S', 'family': 'Abella', 'sequence': 'additional', 'affiliation': []},
{ 'given': 'Angélica Margarita',
'family': 'Portillo-Vázquez',
'sequence': 'additional',
'affiliation': []},
{'given': 'Christopher W', 'family': 'Woods', 'sequence': 'additional', 'affiliation': []},
{'given': 'Adrian F', 'family': 'Hernandez', 'sequence': 'additional', 'affiliation': []},
{'given': 'David R', 'family': 'Boulware', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-7721-6975',
'authenticated-orcid': False,
'given': 'Susanna',
'family': 'Naggie',
'sequence': 'additional',
'affiliation': []},
{'given': 'Radha', 'family': 'Rajasingham', 'sequence': 'additional', 'affiliation': []}],
'member': '239',
'published-online': {'date-parts': [[2023, 6, 16]]},
'reference': [ { 'key': '2023061610301489000_13.6.e065305.1',
'doi-asserted-by': 'crossref',
'first-page': '1897',
'DOI': '10.1001/jama.2020.4742',
'article-title': 'Treating COVID-19—off-label drug use, compassionate use, and randomized '
'clinical trials during Pandemics',
'volume': '323',
'author': 'Kalil',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': '2023061610301489000_13.6.e065305.2',
'doi-asserted-by': 'crossref',
'unstructured': 'McCreary EK , Pogue JM . Pharmacists. Coronavirus disease 2019 '
'treatment: A review of early and emerging options. Open Forum Infect Dis '
'2020;7:ofaa105. doi:10.1093/ofid/ofaa105',
'DOI': '10.1093/ofid/ofaa105'},
{ 'key': '2023061610301489000_13.6.e065305.3',
'doi-asserted-by': 'publisher',
'DOI': '10.1038/s41422-020-0282-0'},
{ 'key': '2023061610301489000_13.6.e065305.4',
'doi-asserted-by': 'crossref',
'first-page': '2030',
'DOI': '10.1056/NEJMoa2022926',
'article-title': 'RECOVERY collaborative group, effect of hydroxychloroquine in '
'hospitalized patients with COVID-19',
'volume': '383',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '2023061610301489000_13.6.e065305.5',
'doi-asserted-by': 'publisher',
'DOI': '10.7326/M20-4207'},
{ 'key': '2023061610301489000_13.6.e065305.6',
'doi-asserted-by': 'crossref',
'first-page': '561',
'DOI': '10.1177/17407745221105106',
'article-title': 'Landscape of Coronavirus disease 2019 clinical trials: new frontiers '
'and challenges',
'volume': '19',
'author': 'Halabi',
'year': '2022',
'journal-title': 'Clin Trials'},
{ 'key': '2023061610301489000_13.6.e065305.7',
'doi-asserted-by': 'crossref',
'first-page': '342',
'DOI': '10.1038/d41586-021-01762-w',
'article-title': 'COVID vaccines to reach poorest countries in 2023—despite recent '
'pledges',
'volume': '595',
'author': 'Padma',
'year': '2021',
'journal-title': 'Nature'},
{ 'key': '2023061610301489000_13.6.e065305.8',
'doi-asserted-by': 'crossref',
'unstructured': 'Nabaggala MS , Nair TS , Gacic-Dobo M , et al . The global inequity in '
'COVID-19 vaccination coverage among health and care workers. Int J '
'Equity Health 2022;21:147. doi:10.1186/s12939-022-01750-0',
'DOI': '10.1186/s12939-022-01750-0'},
{ 'key': '2023061610301489000_13.6.e065305.9',
'unstructured': 'World Health Organization . Prevention, identification and management of '
'health worker infection in the context of COVID-19. 2020. Available: '
'https://www.who.int/publications/i/item/10665-336265'},
{ 'key': '2023061610301489000_13.6.e065305.10',
'unstructured': 'The United Kingdom Office for National Statistics . Coronavirus '
'(COVID-19) infections in the community in England. 2021. Available: '
'https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19infectionsinthecommunityinengland/characteristicsofpeopletestingpositiveforcovid19incountriesoftheuk20may2021#percentage-testing-positive-for-covid-19-by-patient-facing-and-non-patient-facing-job-roles-uk'},
{ 'key': '2023061610301489000_13.6.e065305.11',
'doi-asserted-by': 'crossref',
'first-page': '195',
'DOI': '10.1001/jamainternmed.2020.6319',
'article-title': 'Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure '
'SARS-Cov-2 prophylaxis among health care workers: a randomized clinical '
'trial',
'volume': '181',
'author': 'Abella',
'year': '2021',
'journal-title': 'JAMA Intern Med'},
{ 'key': '2023061610301489000_13.6.e065305.12',
'doi-asserted-by': 'crossref',
'first-page': 'e835',
'DOI': '10.1093/cid/ciaa1571',
'article-title': 'Hydroxychloroquine as pre-exposure prophylaxis for Coronavirus disease '
'2019 (COVID-19) in Healthcare workers: A randomized trial',
'volume': '72',
'author': 'Rajasingham',
'year': '2021',
'journal-title': 'Clin Infect Dis'},
{ 'key': '2023061610301489000_13.6.e065305.13',
'doi-asserted-by': 'crossref',
'first-page': '40',
'DOI': '10.1016/j.ijid.2023.01.019',
'article-title': 'Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health '
'care workers: a randomized, multicenter, placebo-controlled trial '
'Healthcare worker exposure response and outcomes of hydroxychloroquine '
'(HERO-HCQ)',
'volume': '129',
'author': 'Naggie',
'year': '2023',
'journal-title': 'Int J Infect Dis'},
{ 'key': '2023061610301489000_13.6.e065305.14',
'doi-asserted-by': 'crossref',
'unstructured': 'Rojas-Serrano J , Portillo-Vásquez AM , Thirion-Romero I , et al . '
'Hydroxychloroquine for prophylaxis of COVID-19 in health workers: a '
'randomized clinical trial. PLoS One 2022;17:e0261980. '
'doi:10.1371/journal.pone.0261980',
'DOI': '10.1371/journal.pone.0261980'},
{ 'key': '2023061610301489000_13.6.e065305.15',
'doi-asserted-by': 'crossref',
'first-page': '167',
'DOI': '10.1016/j.ijid.2021.12.343',
'article-title': 'Safety and tolerability of hydroxychloroquine in health care workers '
'and first responders for the prevention of COVID-19: WHIP COVID-19 '
'study',
'volume': '116',
'author': 'McKinnon',
'year': '2022',
'journal-title': 'Int J Infect Dis'},
{ 'key': '2023061610301489000_13.6.e065305.16',
'doi-asserted-by': 'publisher',
'DOI': '10.7326/M14-2385'},
{ 'key': '2023061610301489000_13.6.e065305.17',
'doi-asserted-by': 'crossref',
'unstructured': 'Syed F , Hassan M , Arif MA , et al . Pre-exposure prophylaxis with '
'various doses of hydroxychloroquine among Healthcare personnel with '
'high-risk exposure to COVID-19: a randomized controlled trial. Cureus '
'2021;13:e20572. doi:10.7759/cureus.20572',
'DOI': '10.7759/cureus.20572'},
{ 'key': '2023061610301489000_13.6.e065305.18',
'doi-asserted-by': 'crossref',
'unstructured': 'Sterne JAC , Savović J , Page MJ , et al . Rob 2: a revised tool for '
'assessing risk of bias in randomised trials. BMJ 2019:l4898. '
'doi:10.1136/bmj.l4898',
'DOI': '10.1136/bmj.l4898'},
{ 'key': '2023061610301489000_13.6.e065305.19',
'doi-asserted-by': 'crossref',
'unstructured': 'Puhan MA , Schünemann HJ , Murad MH , et al . A GRADE working group '
'approach for rating the quality of treatment effect estimates from '
'network meta-analysis. BMJ 2014;349:g5630. doi:10.1136/bmj.g5630',
'DOI': '10.1136/bmj.g5630'},
{ 'key': '2023061610301489000_13.6.e065305.20',
'doi-asserted-by': 'crossref',
'first-page': '3',
'DOI': '10.1177/1740774520969136',
'article-title': 'Meta-analysis of rare adverse events in randomized clinical trials: '
'Bayesian and Frequentist methods',
'volume': '18',
'author': 'Hong',
'year': '2021',
'journal-title': 'Clin Trials'},
{ 'key': '2023061610301489000_13.6.e065305.21',
'unstructured': 'Watanabe S , Opper M . Asymptotic equivalence of Bayes cross validation '
'and widely applicable information criterion in singular learning theory. '
'J Mach Learn Res 2010;11:12.'},
{ 'key': '2023061610301489000_13.6.e065305.22',
'doi-asserted-by': 'crossref',
'first-page': '550',
'DOI': '10.1016/j.bja.2020.08.062',
'article-title': 'Bayesian predictive probabilities: a good way to monitor clinical '
'trials',
'volume': '126',
'author': 'Ferreira',
'year': '2021',
'journal-title': 'Br J Anaesth'},
{ 'key': '2023061610301489000_13.6.e065305.23',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/sim.1186'},
{ 'key': '2023061610301489000_13.6.e065305.24',
'doi-asserted-by': 'publisher',
'DOI': '10.1136/bmj.315.7109.629'},
{ 'key': '2023061610301489000_13.6.e065305.25',
'unstructured': 'Stan Developent Team . Rstan: the R interface to Stan. R Package Version '
'2020:2.'},
{ 'key': '2023061610301489000_13.6.e065305.26',
'unstructured': 'R Core Team . R: A language and environment for statistical computing. '
'Vienna, Austria: R Foundation for Statistical Computing, 2021.'},
{ 'key': '2023061610301489000_13.6.e065305.27',
'doi-asserted-by': 'crossref',
'first-page': '457',
'DOI': '10.1214/ss/1177011136',
'article-title': 'Inference from Iterative simulation using multiple sequences',
'volume': '7',
'author': 'Gelman',
'year': '1992',
'journal-title': 'Statist Sci'},
{ 'key': '2023061610301489000_13.6.e065305.28',
'doi-asserted-by': 'crossref',
'first-page': '5',
'DOI': '10.1080/14787210.2020.1799785',
'article-title': 'Hydroxychloroquine in the COVID-19 pandemic era: in pursuit of a '
'rational use for prophylaxis of SARS-Cov-2 infection',
'volume': '19',
'author': 'Infante',
'year': '2021',
'journal-title': 'Expert Rev Anti Infect Ther'},
{ 'key': '2023061610301489000_13.6.e065305.29',
'unstructured': 'Revised advisory on the use of hydroxychloroquine (HCQ) as prophylaxis '
'for SARS-Cov-2 infection (in Supersession of previous advisory dated '
'23rd March. 2020. 2022. Available: '
'https://www.icmr.gov.in/pdf/covid/techdoc/V5_Revised_advisory_on_the_use_of_HCQ_SARS_CoV2_infection.pdf'},
{ 'key': '2023061610301489000_13.6.e065305.30',
'doi-asserted-by': 'crossref',
'unstructured': 'Llanos-Cuentas A , Schwalb A , Quintana JL , et al . Hydroxychloroquine '
'to prevent SARS-Cov-2 infection among Healthcare workers: early '
'termination of a phase 3, randomised, open-label, controlled clinical '
'trial. BMC Res Notes 2023;16:22. doi:10.1186/s13104-023-06281-7',
'DOI': '10.1186/s13104-023-06281-7'},
{ 'key': '2023061610301489000_13.6.e065305.31',
'doi-asserted-by': 'crossref',
'unstructured': 'Lofgren SM , Nicol MR , Bangdiwala AS , et al . Safety of '
'hydroxychloroquine among outpatient clinical trial participants for '
'covid-19. Open Forum Infectious Diseases 2020;7. '
'doi:10.1093/ofid/ofaa500',
'DOI': '10.1093/ofid/ofaa500'},
{ 'key': '2023061610301489000_13.6.e065305.32',
'doi-asserted-by': 'crossref',
'first-page': '314',
'DOI': '10.1016/j.ijid.2021.04.035',
'article-title': 'Positive impact of oral hydroxychloroquine and Povidone-iodine throat '
'spray for COVID-19 prophylaxis: an open-label randomized trial',
'volume': '106',
'author': 'Seet',
'year': '2021',
'journal-title': 'Int J Infect Dis'},
{ 'key': '2023061610301489000_13.6.e065305.33',
'doi-asserted-by': 'crossref',
'first-page': '6',
'DOI': '10.1002/jrsm.1153',
'article-title': 'A Bayesian missing data framework for generalized multiple outcome '
'mixed treatment comparisons',
'volume': '7',
'author': 'Hong',
'year': '2016',
'journal-title': 'Res Syn Meth'},
{ 'key': '2023061610301489000_13.6.e065305.34',
'doi-asserted-by': 'publisher',
'DOI': '10.1177/0272989X13481110'},
{ 'key': '2023061610301489000_13.6.e065305.35',
'doi-asserted-by': 'crossref',
'first-page': '789',
'DOI': '10.1007/s10654-022-00891-4',
'article-title': 'Systematic review and meta-analysis of randomized trials of '
'hydroxychloroquine for the prevention of COVID-19',
'volume': '37',
'author': 'García-Albéniz',
'year': '2022',
'journal-title': 'Eur J Epidemiol'},
{ 'key': '2023061610301489000_13.6.e065305.36',
'doi-asserted-by': 'crossref',
'unstructured': 'Tirupakuzhi Vijayaraghavan BK , Jha V , Rajbhandari D , et al . '
'Hydroxychloroquine plus personal protective equipment versus personal '
'protective equipment alone for the prevention of laboratory-confirmed '
'COVID-19 infections among Healthcare workers: a Multicentre, '
'parallel-group randomised controlled trial from India. BMJ Open '
'2022;12:e059540. doi:10.1136/bmjopen-2021-059540',
'DOI': '10.1136/bmjopen-2021-059540'},
{ 'key': '2023061610301489000_13.6.e065305.37',
'doi-asserted-by': 'crossref',
'first-page': '85',
'DOI': '10.1016/j.cmi.2022.07.006',
'article-title': 'Daily tenofovir disoproxil fumarate/Emtricitabine and '
'hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a '
'double-blind placebo-controlled randomized trial in Healthcare workers',
'volume': '29',
'author': 'Polo',
'year': '2023',
'journal-title': 'Clin Microbiol Infect'},
{ 'key': '2023061610301489000_13.6.e065305.38',
'doi-asserted-by': 'crossref',
'unstructured': 'Grau-Pujol B , Camprubí-Ferrer D , Marti-Soler H , et al . Pre-exposure '
'prophylaxis with hydroxychloroquine for COVID-19: a double-blind, '
'placebo-controlled randomized clinical trial. Trials 2021;22:808. '
'doi:10.1186/s13063-021-05758-9',
'DOI': '10.1186/s13063-021-05758-9'}],
'container-title': 'BMJ Open',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1136/bmjopen-2022-065305',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 6, 16]],
'date-time': '2023-06-16T17:34:19Z',
'timestamp': 1686936859000},
'score': 1,
'resource': {'primary': {'URL': 'https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-065305'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2023, 6]]},
'references-count': 38,
'journal-issue': { 'issue': '6',
'published-online': {'date-parts': [[2023, 6, 16]]},
'published-print': {'date-parts': [[2023, 6]]}},
'alternative-id': ['10.1136/bmjopen-2022-065305'],
'URL': 'http://dx.doi.org/10.1136/bmjopen-2022-065305',
'relation': {},
'ISSN': ['2044-6055', '2044-6055'],
'subject': ['General Medicine'],
'container-title-short': 'BMJ Open',
'published': {'date-parts': [[2023, 6]]}}
