Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study
Mehmet Ozgur Sogut, Mehmet Mustafa Can, Ramazan Guven, Onur Kaplan, Hüseyin Ergenc, Tuba Betül Umit, Olgun Demir, Murat Kaya, Tarık Akdemir, Sümeyye Cakmak
The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Conflict of interests None. All authors have read and approved the submitted manuscript. This manuscript has not been submitted nor published elsewhere in whole or in part.
Author contributions Ö J o u r n a l P r e -p r o o f
References
Bazett, An analysis of the time-relationships of electrocardiograms, Heart
Bedford, Enria, Giesecke, COVID-19: towards controlling of a pandemic, Lancet
Boulware, Pullen, Bangdiwala, A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19, N Engl J Med
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19, N Engl J Med
Chatre, Roubille, Vernhet, Jorgensen, Pers, Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature, Drug Saf
Gao, Tian, Xu, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends
Gautret, Lagier, Parola, Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study, Travel Med Infect Dis
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Geleris, Sun, Platt, Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med
Geleris, Sun, Platt, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Giudicessi, Noseworthy, Friedman, Ackerman, Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19), Mayo Clin Proc
Guo, Cao, Hong, The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak -an update on the status, Mil Med Res
Huang, Wang, Li, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Jin, Cai, Cheng, A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version), Mil Med Res
Kashour, Riaz, Garbati, Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis, J Antimicrob Chemother
Li, Clercq, Therapeutic options for the 2019 novel coronavirus (2019-nCoV), Nat Rev Drug Discov
Malviya, Ventricular arrhythmia risk due to chloroquine / hydroxychloroquine treatment for COVID-19: Should it be given, Indian Heart J
Matthieu, Viet-Thi, Mathilde, Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data, BMJ
Mcghie, Harvey, Su, Anderson, Tomlinson et al., Electrocardiogram abnormalities related to anti-malarials in systemic lupus erythematosus, Clin Exp Rheumatol
Naksuk, Lazar, Peeraphatdit, Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol, Eur Heart J Acute Cardiovasc Care
Page, Bryant, Cheng, Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association, Circulation
Rosenberg, Dufort, Udo, Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State, JAMA
Simpson, Kovacs, Stecker, Ventricular arrhythmia risk due to hydroxychloroquine-azithromycin treatment for COVID-19, Cardiol Mag
Tang, Cao, Han, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Tisdale, Jayes, Kingery, Development and validation of a risk score to predict QT interval prolongation in hospitalized patients, Circ Cardiovasc Qual Outcomes
Young, Ong, Kalimuddin, Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore, JAMA
Zhou, Dai, Tong, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression, J Antimicrob Chemother
{ 'indexed': {'date-parts': [[2024, 3, 12]], 'date-time': '2024-03-12T02:39:28Z', 'timestamp': 1710211168632},
'reference-count': 30,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2021, 2, 1]],
'date-time': '2021-02-01T00:00:00Z',
'timestamp': 1612137600000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}],
'funder': [{'name': 'University Board of Scientific Research Projects', 'award': ['108']}],
'content-domain': { 'domain': [ 'clinicalkey.jp', 'clinicalkey.com', 'clinicalkey.es', 'clinicalkey.com.au',
'clinicalkey.fr', 'elsevier.com', 'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2021, 2]]},
'DOI': '10.1016/j.ajem.2020.12.014',
'type': 'journal-article',
'created': { 'date-parts': [[2020, 12, 11]],
'date-time': '2020-12-11T22:59:39Z',
'timestamp': 1607727579000},
'page': '41-46',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 20,
'title': 'Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot '
'observational study',
'prefix': '10.1016',
'volume': '40',
'author': [ {'given': 'Ozgur', 'family': 'Sogut', 'sequence': 'first', 'affiliation': []},
{'given': 'Mehmet Mustafa', 'family': 'Can', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ramazan', 'family': 'Guven', 'sequence': 'additional', 'affiliation': []},
{'given': 'Onur', 'family': 'Kaplan', 'sequence': 'additional', 'affiliation': []},
{'given': 'Hüseyin', 'family': 'Ergenc', 'sequence': 'additional', 'affiliation': []},
{'given': 'Tuba Betül', 'family': 'Umit', 'sequence': 'additional', 'affiliation': []},
{'given': 'Olgun', 'family': 'Demir', 'sequence': 'additional', 'affiliation': []},
{'given': 'Murat', 'family': 'Kaya', 'sequence': 'additional', 'affiliation': []},
{'given': 'Tarık', 'family': 'Akdemir', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sümeyye', 'family': 'Cakmak', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'reference': [ { 'key': '10.1016/j.ajem.2020.12.014_bb0005',
'doi-asserted-by': 'crossref',
'first-page': '497',
'DOI': '10.1016/S0140-6736(20)30183-5',
'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in '
'Wuhan, China',
'volume': '395',
'author': 'Huang',
'year': '2020',
'journal-title': 'Lancet'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0010',
'doi-asserted-by': 'crossref',
'first-page': '101663',
'DOI': '10.1016/j.tmaid.2020.101663',
'article-title': 'Clinical and microbiological effect of a combination of '
'hydroxychloroquine and azithromycin in 80 COVID-19 patients with at '
'least a six-day follow up: a pilot observational study',
'volume': '34',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0020',
'doi-asserted-by': 'crossref',
'first-page': '1015',
'DOI': '10.1016/S0140-6736(20)30673-5',
'article-title': 'COVID-19: towards controlling of a pandemic',
'volume': '395',
'author': 'Bedford',
'year': '2020',
'journal-title': 'Lancet'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0025',
'author': 'T. C. Ministry Of Health General Directorate Of Public Health'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0030',
'doi-asserted-by': 'crossref',
'first-page': '1488',
'DOI': '10.1001/jama.2020.3204',
'article-title': 'Epidemiologic features and clinical course of patients infected with '
'SARS-CoV-2 in Singapore',
'volume': '323',
'author': 'Young',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0035',
'doi-asserted-by': 'crossref',
'first-page': '149',
'DOI': '10.1038/d41573-020-00016-0',
'article-title': 'Therapeutic options for the 2019 novel coronavirus (2019-nCoV)',
'volume': '19',
'author': 'Li',
'year': '2020',
'journal-title': 'Nat Rev Drug Discov'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0040',
'first-page': '11',
'article-title': 'The origin, transmission and clinical therapies on coronavirus disease '
'2019 (COVID-19) outbreak - an update on the status',
'volume': '7',
'author': 'Guo',
'year': '2020',
'journal-title': 'Mil Med Res'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0045',
'doi-asserted-by': 'crossref',
'first-page': '105949',
'DOI': '10.1016/j.ijantimicag.2020.105949',
'article-title': 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results '
'of an open-label non-randomized clinical trial',
'volume': '56',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0050',
'first-page': '4',
'article-title': 'A rapid advice guideline for the diagnosis and treatment of 2019 novel '
'coronavirus (2019-nCoV) infected pneumonia (standard version)',
'volume': '7',
'author': 'Jin',
'year': '2020',
'journal-title': 'Mil Med Res'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0055',
'article-title': 'Ventricular arrhythmia risk due to hydroxychloroquine-azithromycin '
'treatment for COVID-19',
'author': 'Simpson',
'year': '2020',
'journal-title': 'Cardiol Mag'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0060',
'doi-asserted-by': 'crossref',
'first-page': '479',
'DOI': '10.1161/CIRCOUTCOMES.113.000152',
'article-title': 'Development and validation of a risk score to predict QT interval '
'prolongation in hospitalized patients',
'volume': '6',
'author': 'Tisdale',
'year': '2013',
'journal-title': 'Circ Cardiovasc Qual Outcomes'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0065',
'first-page': '35',
'article-title': 'An analysis of the time-relationships of electrocardiograms',
'volume': '7',
'author': 'Bazett',
'year': '1920',
'journal-title': 'Heart'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0080',
'doi-asserted-by': 'crossref',
'first-page': '215',
'DOI': '10.1177/2048872620922784',
'article-title': 'Cardiac safety of off-label COVID-19 drug therapy: a review and '
'proposed monitoring protocol',
'volume': '9',
'author': 'Naksuk',
'year': '2020',
'journal-title': 'Eur Heart J Acute Cardiovasc Care'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0085',
'doi-asserted-by': 'crossref',
'first-page': '919',
'DOI': '10.1007/s40264-018-0689-4',
'article-title': 'Cardiac complications attributed to chloroquine and hydroxychloroquine: '
'a systematic review of the literature',
'volume': '41',
'author': 'Chatre',
'year': '2018',
'journal-title': 'Drug Saf'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0095',
'doi-asserted-by': 'crossref',
'first-page': '131',
'DOI': '10.1016/j.ihj.2020.04.006',
'article-title': 'Ventricular arrhythmia risk due to chloroquine / hydroxychloroquine '
'treatment for COVID-19: should it be given',
'volume': '72',
'author': 'Malviya',
'year': '2020',
'journal-title': 'Indian Heart J'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0100',
'doi-asserted-by': 'crossref',
'first-page': 'e32e69',
'DOI': '10.1161/CIR.0000000000000426',
'article-title': 'Drugs that may cause or exacerbate heart failure: a scientific '
'statement from the American Heart Association',
'volume': '134',
'author': 'Page',
'year': '2016',
'journal-title': 'Circulation'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0105',
'doi-asserted-by': 'crossref',
'first-page': '1213',
'DOI': '10.1016/j.mayocp.2020.03.024',
'article-title': 'Urgent guidance for navigating and circumventing the QTc-prolonging and '
'Torsadogenic potential of possible pharmacotherapies for coronavirus '
'disease 19 (COVID-19)',
'volume': '95',
'author': 'Giudicessi',
'year': '2020',
'journal-title': 'Mayo Clin Proc'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0110',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.tmaid.2020.101735',
'article-title': 'Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and '
'other viral infections: A narrative review',
'author': 'Hashem',
'year': '2020',
'journal-title': 'Travel Med Infect Dis'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0115',
'doi-asserted-by': 'crossref',
'first-page': '2041',
'DOI': '10.1056/NEJMoa2019014',
'article-title': 'Hydroxychloroquine with or without azithromycin in mild-to-moderate '
'Covid-19',
'volume': '383',
'author': 'Cavalcanti',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0120',
'doi-asserted-by': 'crossref',
'first-page': '2411',
'DOI': '10.1056/NEJMoa2012410',
'article-title': 'Observational study of hydroxychloroquine in hospitalized patients with '
'Covid-19',
'volume': '382',
'author': 'Geleris',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0125',
'doi-asserted-by': 'crossref',
'first-page': '2493',
'DOI': '10.1001/jama.2020.8630',
'article-title': 'Association of treatment with hydroxychloroquine or azithromycin with '
'in-hospital mortality in patients with COVID-19 in New York State',
'volume': '323',
'author': 'Rosenberg',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0130',
'doi-asserted-by': 'crossref',
'first-page': '517',
'DOI': '10.1056/NEJMoa2016638',
'article-title': 'A randomized trial of hydroxychloroquine as postexposure prophylaxis '
'for Covid-19',
'volume': '383',
'author': 'Boulware',
'year': '2020',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0135',
'doi-asserted-by': 'crossref',
'first-page': 'm1849',
'DOI': '10.1136/bmj.m1849',
'article-title': 'Hydroxychloroquine in patients with mainly mild to moderate coronavirus '
'disease 2019: open label, randomised controlled trial',
'volume': '369',
'author': 'Tang',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0140',
'article-title': 'Efficacy of hydroxychloroquine in patients with COVID-19: results of a '
'randomized clinical trial',
'author': 'Chen',
'year': '2020',
'journal-title': 'MedRxiv'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0145',
'doi-asserted-by': 'crossref',
'first-page': '72',
'DOI': '10.5582/bst.2020.01047',
'article-title': 'Breakthrough: chloroquine phosphate has shown apparent efficacy in '
'treatment of COVID-19 associated pneumonia in clinical studies',
'volume': '14',
'author': 'Gao',
'year': '2020',
'journal-title': 'Biosci Trends'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0150',
'doi-asserted-by': 'crossref',
'first-page': '1667',
'DOI': '10.1093/jac/dkaa114',
'article-title': 'COVID-19: a recommendation to examine the effect of hydroxychloroquine '
'in preventing infection and progression',
'volume': '75',
'author': 'Zhou',
'year': '2020',
'journal-title': 'J Antimicrob Chemother'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0155',
'doi-asserted-by': 'crossref',
'first-page': '30',
'DOI': '10.1093/jac/dkaa403',
'article-title': 'Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a '
'systematic review and meta-analysis',
'volume': '76',
'author': 'Kashour',
'year': '2021',
'journal-title': 'J Antimicrob Chemother'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0160',
'first-page': 'm1844',
'article-title': 'Clinical efficacy of hydroxychloroquine in patients with covid-19 '
'pneumonia who require oxygen: observational comparative study using '
'routine care data',
'volume': '369',
'author': 'Matthieu',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0165',
'first-page': '545',
'article-title': 'Electrocardiogram abnormalities related to anti-malarials in systemic '
'lupus erythematosus',
'volume': '36',
'author': 'McGhie',
'year': '2018',
'journal-title': 'Clin Exp Rheumatol'},
{ 'key': '10.1016/j.ajem.2020.12.014_bb0170',
'doi-asserted-by': 'crossref',
'first-page': '521',
'DOI': '10.1191/0961203306lu2345oa',
'article-title': 'The cardiac safety of chloroquine phosphate treatment in patients with '
'systemic lupus erythematosus: the influence on arrhythmia, heart rate '
'variability and repolarization parameters',
'volume': '15',
'author': 'Wozniacka',
'year': '2006',
'journal-title': 'Lupus'}],
'container-title': 'The American Journal of Emergency Medicine',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S0735675720311335?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S0735675720311335?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2021, 3, 8]],
'date-time': '2021-03-08T05:54:11Z',
'timestamp': 1615182851000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S0735675720311335'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 2]]},
'references-count': 30,
'alternative-id': ['S0735675720311335'],
'URL': 'http://dx.doi.org/10.1016/j.ajem.2020.12.014',
'relation': {},
'ISSN': ['0735-6757'],
'subject': [],
'container-title-short': 'The American Journal of Emergency Medicine',
'published': {'date-parts': [[2021, 2]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed '
'COVID-19: A pilot observational study',
'name': 'articletitle',
'label': 'Article Title'},
{ 'value': 'The American Journal of Emergency Medicine',
'name': 'journaltitle',
'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.ajem.2020.12.014',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': '© 2020 Elsevier Inc. All rights reserved.',
'name': 'copyright',
'label': 'Copyright'}]}