LB-17 - Efficacy of Hydroxychloroquine (HCQ) for Post-exposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Blinded, Randomized, Controlled Trial

Background: Prevention interventions for coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are currently limited to non-pharmaceutical strategies. Observational and laboratory data suggested that hydroxychloroquine (HCQ) had biologic activity against SARS-CoV-2. A blinded trial of HCQ in persons with confirmed exposure and virologic and clinical endpoints is needed.

Methods: We conducted a national, householdrandomized, double-blind, controlled trial of HCQ post-exposure prophylaxis, with entirely remote study procedures. We enrolled close contacts exposed to persons with SARS-CoV-2 infection in the past 96 hours. Participants were randomized to either HCQ (400 mg daily for three days followed by 200 mg daily for eleven days) or ascorbic acid (500 mg followed by 250 mg daily), as a placebo-equivalent control. Participants self-collected mid-turbinate swabs daily (days 1-14) for SARS-CoV-2 PCR testing. The primary outcome was PCR-confirmed, incident SARS-CoV-2 infection among persons SARS-CoV-2 negative at enrollment. Symptoms were assessed using criteria from the US CDC.

Results: From March-August 2020, 623 households were randomized; 311 households (381 participants) to the HCQ group and 312 households (400 participants) to the control group. Ninety- one percent of participants were retained up to day 14 and 9,595 of 10,588 (91%) of swabs were tested. Among participants who were SARS-CoV-2 negative at baseline (n=626/781, 80%), the cumulative incidence of  SARS-CoV-2 was 14.5% (95% CI: 11.6-17.4) and the cumulative incidence of COVID-19 symptoms was 11.6% (95% CI: 8.9-14.2) at day 14. By day 14, there was no difference between the HCQ group and control group in SARS-CoV-2 acquisition (46 vs. 43 events, aHR= 0.99, 95% CI 0.64-1.52, p=0.95) or symptomatic disease (40 vs. 32 events, aHR= 1.23, 95% CI: 0.76-1.99, p=0.40). The adverse event frequency was similar between groups (59 [15.5%] participants in the HCQ and 45 [11.3%] in the control group, p=0.092).Cumulative incidence of RT-PCR-confirmed SARS-CoV-2 infection among close contacts of diagnosed cases, by study group


Conclusion: This randomized, double-blind, controlled trial among persons with recent exposure and high incidence of SAR-CoV2 provides strong evidence that HCQ post-exposure prophylaxis did not prevent SARS-CoV-2 infection or modify clinical disease.

Presenter and Author(s)

• 

  Ruanne V. Barnabas, MBChB, MSc, DPhil

  Associate Professor
  University of Washington
  Seattle, WA

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

  Slides

Co-Author(s)

• EB

  Elizabeth R. Brown, ScD

  Research Professor, Biostatistics
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AB

  Anna Bershteyn, PhD

  Assistant Professor
  New York University Grossman School of Medicine
  New York, New York

  Disclosure: Bill and Melinda Gates Foundation (Grant/Research Support)Gates Ventures (Consultant)National Institutes of Health (Grant/Research Support)
• HS

  Helen C. Stankiewicz Karita, MD, MS

  Acting Instructor, Infectious Diseases
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• CJ

  Christine Johnston, MD, MPH

  Associate Professor
  University of Washington
  Seattle, WA

  Disclosure: No Disclosure
• LT

  Lorna Thorpe, MPH, PhD

  Professor
  New York University Grossman School of Medicine
  New York, New York

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AK

  Angelica Kottkamp, MD

  Instructor
  New York University Grossman School of Medicine
  New York, New York

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• KN

  Kathleen Neuzil, MD, MPH

  Professor
  University of Maryland School of Medicine
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• ML

  Miriam K. Laufer, MD

  Professor
  University of Maryland School of Medicine
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MD

  Meagan Deming, MD, PhD

  Fellow
  Center for Vaccine Development, University of Maryland Medical Center
  Baltimore, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MP

  Michael K. Paasche-Orlow, MD

  Associate Professor of Medicine
  Boston University School of Medicine
  Boston, Massachusetts

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• PK

  Patricia J. Kissinger, PhD, MPH

  Professor
  School of Medicine, Tulane University
  New Orleans, Louisiana

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AL

  Alfred Luk, MD

  Attending Physician
  Tulane University
  New Orleans, NY

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• KP

  Kristopher M. Paolino, MD, MTM&H

  Assistant Professor
  State University of New York Upstate Medical University
  Syracuse, New York

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• RL

  Raphael J. Landovitz, MD, MSc

  Professor of Medicine
  UCLA Center for Clinical AIDS Research & Education
  Los Angeles, California

  Disclosure: Gilead (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Other Financial or Material Support, Speaker Honoraria)
• RH

  Risa Hoffman, MD

  Associate Clinical Professor
  University of California
  Los Angeles, California

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• TS

  Torin Schaafsma, MPH

  Data Manager & Analyst
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MK

  Meighan L. Krows, BA

  International Research Manager
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• KT

  Katherine Thomas, MSc

  Director of Biostatistics
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• SM

  Susan Morrison, MD, MPH

  Research Coordinator
  Unviersity of Washinton
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• LK

  Lara Kidoguchi, MPH

  Data Manager, Safety
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MW

  Mark H. Wener, MD

  Professor
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AG

  Alexander L. Greninger, MD, PhD

  Professor
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MH

  Meei-Li Huang, PhD

  Research Scientist
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• KJ

  Keith Jerome, MD, PhD

  Professor
  University of Washington
  Seattle, WA

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  Anna Wald, MD, MPH

  Professor of Medicine
  University of Washington
  Seattle, Washington

  Disclosure: Aicuris : Consultant (Status: Ongoing); Gilead : Consultant (Status: Ongoing); GlaxoSmithKline : Scientific Research Study Investigator (Status: Ongoing); Merck : DSMB participation; provision of vaccine for a study (Status: Ongoing), Other Financial or Material Support (Status: Ongoing); Sanofi : Scientific Research Study Investigator (Status: Ongoing); X-Vax : Consultant (Status: Ongoing)
• CC

  Connie Celum, MD, MPH

  Professor
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  Helen Y. Chu, MD MPH

  Assistant Professor
  University of Washington
  Seattle, WA

  Disclosure: Cepheid (Grant/Research Support)Ellume (Grant/Research Support)Glaxo Smith Kline (Consultant)Merck (Consultant)Sanofi-Pasteur (Grant/Research Support)
• JB

  Jared M. Baeten, MD, PhD

  Professor
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.