TITLE: High-dose Hydroxychloroquine for Mild COVID-19: One Center’s Clinical Experience and Investigational Challenges

AUTHORS: Iazsmin Bauer Ventura, MD MSc; Brian W. Labadie, MD; Patrick Onkka, MD; Pankti Reid, MD; Moira McNulty, MD; Cuoghi Edens, MD; David G. Beiser, MD MS; Mark Ratain, MD; Reem Jan, MBBS BSc

AFFILIATIONS: University of Chicago, Department of Medicine, Section of Rheumatology (IBV, PR, CE, RJ); University of Chicago, Department of Medicine (BL); University of Chicago, Department of Medicine, Section of Infectious Diseases & Global Health (MM); University of Chicago, Department of Pediatrics, Section of Pediatric Rheumatology (CE); University of Chicago, Department of Emergency Medicine (DGB); University of Chicago, Department of Medicine, Section of Hematology and Oncology (MR); Northwestern Medical Group (PO)

CORRESPONDING AUTHOR:

Iazsmin Bauer Ventura

5841 South Maryland Avenue, N005D

Chicago, IL 60637

email: Iazsmin.ventura@uchospitals.edu

PRINCIPAL INVESTIGATOR STATEMENT: The authors confirm that the Principal Investigator for this paper is Dr. Reem Jan and that she has direct clinical responsibility for the patients included in this study.

AUTHORSHIP STATEMENT: All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the concept, design analysis, writing, or revision of the manuscript. Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication before its appearance in the British Journal of Clinical Pharmacology.

CONFLICT OF INTEREST DISCLOSURE: The authors whose names are listed above certify that they have NO affiliations with or involvement in any organizations or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.

ETHICS APPROVAL STATEMENT/ PERSONAL COSENT STATEMENT: This study was approved by the University of Chicago Institutional Review of Boards and all patients included in this study signed a consent form.

DATA AVAILABILITY STATEMENT: The data that supports the findings of this study are available on request from the corresponding author (IBV). The data are not publicly available due to their containing information that could compromise the privacy of research participants.

FUNDING STATEMENT: This study did not receive any funding outside the University of Chicago.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04351620

KEY WORDS: hydroxychloroquine, SARS-CoV-2, COVID-19, clinical trial, tolerability, review.

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ABSTRACT:

Aims: The recently described SARS-CoV-2 has led to a pandemia which has severe consequences for the global community. Hydroxychloroquine has been repurposed for the treatment of COVID-19 but conflicting information on its efficacy and safety has since emerged. Our group designed a trial on the use of high-dose hydroxychloroquine in a high-risk ambulatory population with mild COVID-19 (NCT04351620) and summarizes herein the clinical data of hydroxychloroquine in COVID-19.

Methods: Single-arm and single-center study evaluating the tolerability of high-dose hydroxychloroquine, 600 mg twice daily for 5 days, in patients with mild COVID-19 and risk factors for clinical decompensation and hospitalization. Secondary objectives included maintenance of ambulatory status, defervescence, and symptom relief.

Results: Over a six-week period, 59 patients met eligibility criteria out of 314 contacted (18.7%). Out of these 59 potentially eligible patients, 44 (74.5%) patients declined to be screened further due to concerns about its risks and unproven efficacy, referencing media accounts and politization of the medication. Out of the 9 patients consented, 2 did not complete the therapy plan, 1 due to headaches, 1 did not follow up. Two of the 7 patients who completed the study continued to have fevers, one was admitted for pneumonia. Study was terminated early due to recruitment difficulties.

Conclusions: The trial met pre-defined primary outcome of tolerability, but sample size was too small to allow further interpretation. The political climate and media coverage might have negatively impacted patient recruitment, which has ultimately led to its early interruption.

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