tetano
Editor, Senior Moderator
JAMA Intern Med
. 2020 Sep 30.
doi: 10.1001/jamainternmed.2020.6319. Online ahead of print.
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial
Benjamin S Abella[SUP] 1 [/SUP], Eliana L Jolkovsky[SUP] 1 [/SUP], Barbara T Biney[SUP] 1 [/SUP], Julie E Uspal[SUP] 1 [/SUP], Matthew C Hyman[SUP] 2 [/SUP], Ian Frank[SUP] 3 [/SUP], Scott E Hensley[SUP] 4 [/SUP], Saar Gill[SUP] 5 [/SUP], Dan T Vogl[SUP] 5 [/SUP], Ivan Maillard[SUP] 5 [/SUP], Daria V Babushok[SUP] 5 [/SUP], Alexander C Huang[SUP] 5 [/SUP], Sunita D Nasta[SUP] 5 [/SUP], Jennifer C Walsh[SUP] 5 [/SUP], E Paul Wiletyo[SUP] 6 [/SUP], Phyllis A Gimotty[SUP] 6 [/SUP], Michael C Milone[SUP] 7 [/SUP], Ravi K Amaravadi[SUP] 5 [/SUP], and the Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators
Affiliations
Abstract
Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk.
Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy.
Design, setting, and participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks.
Main outcomes and measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants.
Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered.
Conclusions and relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.
Trial registration: ClinicalTrials.gov Identifier: NCT04329923.
. 2020 Sep 30.
doi: 10.1001/jamainternmed.2020.6319. Online ahead of print.
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial
Benjamin S Abella[SUP] 1 [/SUP], Eliana L Jolkovsky[SUP] 1 [/SUP], Barbara T Biney[SUP] 1 [/SUP], Julie E Uspal[SUP] 1 [/SUP], Matthew C Hyman[SUP] 2 [/SUP], Ian Frank[SUP] 3 [/SUP], Scott E Hensley[SUP] 4 [/SUP], Saar Gill[SUP] 5 [/SUP], Dan T Vogl[SUP] 5 [/SUP], Ivan Maillard[SUP] 5 [/SUP], Daria V Babushok[SUP] 5 [/SUP], Alexander C Huang[SUP] 5 [/SUP], Sunita D Nasta[SUP] 5 [/SUP], Jennifer C Walsh[SUP] 5 [/SUP], E Paul Wiletyo[SUP] 6 [/SUP], Phyllis A Gimotty[SUP] 6 [/SUP], Michael C Milone[SUP] 7 [/SUP], Ravi K Amaravadi[SUP] 5 [/SUP], and the Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators
Affiliations
- PMID: 33001138
- DOI: 10.1001/jamainternmed.2020.6319
Abstract
Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk.
Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy.
Design, setting, and participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks.
Main outcomes and measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants.
Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered.
Conclusions and relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.
Trial registration: ClinicalTrials.gov Identifier: NCT04329923.