Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial

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Abstract

Background

Older patients are at risk of increased morbidity and mortality from COVID-19 disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are few effective treatments for outpatients with COVID-19.

Objective

To evaluate the efficacy of hydroxychloroquine to reduce time in quarantine for symptomatic ≥40 years-old COVID-19 patients.

Design

A randomized, double-blind, placebo-controlled clinical trial.

Setting

Outpatients with polymerase chain reaction confirmed COVID-19 at a University of Pennsylvania affiliated testing center between April 15, 2020 and, July 14, 2020.

Participants

Out of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephone-based recruitment, but only 34 subjects were able to be randomized.

Interventions

Hydroxychloroquine 400 mg per twice daily (n=17) or matching placebo (n=17), taken orally for up to 14 days.

Measurements

The primary outcome was the time to release from quarantine. Secondary outcomes included the participant-reported secondary infection of co-inhabitants, hospitalization, treatment-related adverse events, time to symptom improvement, and incidence of cardiac arrhythmia.

Results

The median time to release from quarantine for HCQ-treated vs. placebo-treated participants was 8 days (range 4-19 days) vs. 11 days (4-18 days); z-score +0.58, p=n.s. This did not meet the pre-specified criteria for early termination, however, this study was terminated early due to lack of feasibility. There was no mortality in either study arm.

Limitation

Since this study was terminated early due to a lack of feasibility, no conclusion can be made about the efficacy of hydroxychloroquine as a treatment for COVID-19 patients 40 years of age or older quarantined at home.

Conclusion

The design of this remotely conducted study could guide testing of other more promising agents during the COVID-19 pandemic.

Trial registration

Clinicaltrials.gov identifier: NCT04329923

Article activity feed

  1. SciScore for 10.1101/2021.02.22.21252228: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was obtained from all subjects via direct communication with study physician via an internet document signature program (DocuSign).
    IRB: Approval for the study was granted by the University of Pennsylvania Institutional Review Board, and the trial was registered on clinicaltrials.gov (NCT04329923).
    RandomizationSubjects were randomized to either HCQ or placebo in blocks of 8, using established randomization software (SealedEnvelope.com, Clerkenwell Workshops).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Subjects completed a daily electronic survey via email (REDCap) to track symptoms, fever, and pill compliance.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04329923TerminatedThe PATCH Trial (Prevention And Treatment of COVID-19 With H…
    NCT04329923TerminatedThe PATCH Trial (Prevention And Treatment of COVID-19 With H…


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.