Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial | Infectious Diseases | JAMA Internal Medicine | JAMA Network
[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    3 Comments for this article
    Why is zinc excluded?
    Jon Noneya, BS | N/A
    From what I understand HCQ is simply an ionophore for the transmission of Zinc across the cell membrane and it's actually the ZINC that stops the replication of the virus. So why is ZINC continually omitted from these studies?
    Zinc Exclusion?
    Philip Mitchell, MD |
    It would be helpful  to hear from the authors about the absence of zinc from the trial.  Zinc in common supplementary doses is very benign. Could they share their reason(s) for not using it? 
    Zinc and HCQ
    Benjamin Abella, MD MPhil | University of Pennsylvania
    Thanks for the questions about zinc as a potential prophylaxis agent. To pursue the most rigorous design to test hydroxychloroquine, we did not want to add a second agent - if we did, we wouldn't know which drug was the key effector.

    Second - I am not aware of any data in support of zinc for COVID-19 prophylaxis - it is perhaps worthy of study, but statements to its potential effectiveness I believe are premature based on the data currently available.
    CONFLICT OF INTEREST: lead author of study
    Original Investigation
    September 30, 2020

    Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial

    Author Affiliations
    • 1Department of Emergency Medicine, University of Pennsylvania, Philadelphia
    • 2Division of Cardiology, Department of Medicine University of Pennsylvania, Philadelphia
    • 3Division of Infectious Disease, Department of Medicine University of Pennsylvania, Philadelphia
    • 4Department of Microbiology, University of Pennsylvania, Philadelphia
    • 5Abramson Cancer Center and Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia
    • 6Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia
    • 7Department of Pathology, University of Pennsylvania, Philadelphia
    JAMA Intern Med. Published online September 30, 2020. doi:10.1001/jamainternmed.2020.6319
    Visual Abstract. Efficacy of Hydroxychloroquine vs Placebo for Pre-Exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
    Efficacy of Hydroxychloroquine vs Placebo for Pre-Exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
    Key Points

    Question  Does a regimen of hydroxychloroquine, 600 mg, per day, reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pre-exposure prophylaxis strategy when taken by hospital-based health care workers?

    Finding  In this double-blind, placebo-controlled randomized clinical trial that included 132 participants and was terminated early, there was not a significant difference in reverse-transcriptase polymerase chain reaction–confirmed SARS-CoV-2 incidence between hydroxychloroquine and placebo cohorts.

    Meaning  Among hospital-based health care workers, daily hydroxychloroquine did not prevent SARS-CoV-2 infection, although the trial was terminated early and may have been underpowered to detect a clinically important difference.


    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