Hydroxychloroquine for COVID-19 Post-exposure Prophylaxis (PEP)

• ClinicalTrials.gov Identifier: NCT04328961
• Recruitment Status: Completed
• First Posted: April 1, 2020
• Results First Posted: December 16, 2021
• Last Update Posted: December 16, 2021
• Sponsor: University of Washington
• Collaborator: Bill and Melinda Gates Foundation
• Information provided by (Responsible Party): Ruanne Barnabas, University of Washington

Tracking Information

• First Submitted Date: March 23, 2020
• First Posted Date: April 1, 2020
• Results First Submitted Date: October 8, 2021
• Results First Posted Date: December 16, 2021
• Last Update Posted Date: December 16, 2021
• Actual Study Start Date: March 31, 2020
• Actual Primary Completion Date: September 24, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2021)

• Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection [ Time Frame: Day 1 through Day 14 after enrolment ]
  Polymerase chain reaction (PCR) confirmed severe acute respiratory syndrome coronavirus 2 of the genus Betacoronavirus (SARS-CoV-2) infection from self-collected samples collected daily for 14 days
• The Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection [ Time Frame: Day 28 after enrolment ]
  Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit

Original Primary Outcome Measures (submitted: March 29, 2020)

• Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection [ Time Frame: Day 1 through Day 14 after enrolment ]
  Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected daily for 14 days
• Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection [ Time Frame: Day 28 after enrolment ]
  Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit

Current Secondary Outcome Measures (submitted: December 14, 2021)

• Rate of Participant-reported Adverse Events [ Time Frame: 28 days from start of Hydroxychloroquine therapy ]
  Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults
• Number of Participants Who Had COVID-19 Disease [ Time Frame: 28 days from enrolment ]
  Participants who had a PCR-confirmed SARS-CoV-2 infection and met the Center for Disease Control (CDC) defined criteria for symptomatic COVID-19 disease.

Original Secondary Outcome Measures (submitted: March 29, 2020)

• Rate of participant-reported adverse events [ Time Frame: 28 days from start of Hydroxychloroquine therapy ]
  Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults
• Incidence rates of COVID-19 through study completion [ Time Frame: 28 days from enrolment ]
  PCR-confirmed COVID-19 diagnosis

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hydroxychloroquine for COVID-19 Post-exposure Prophylaxis (PEP)
• Official Title: Efficacy of Hydroxychloroquine for Post-exposure Prophylaxis (PEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Adults Exposed to Coronavirus Disease (COVID-19): a Blinded, Randomized Study
• Brief Summary: This is a clinical study for the prevention of SARS-CoV-2 infection in adults exposed to the virus. This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) who are close contacts of persons with laboratory confirmed SARS-CoV-2 or clinically suspected COVID-19. Eligible participants will be enrolled and randomized to receive the intervention or placebo at the level of the household (all eligible participants in one household will receive the same intervention).
• Detailed Description: This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of Hydroxychloroquine (HCQ) post-exposure prophylaxis (PEP) for the prevention of SARS-CoV-2 infection in adults exposed to the virus.The overarching goal of this study is to assess the effectiveness of HCQ PEP on the incidence of SARS-CoV-2 detection by polymerase chain reaction (PCR) to inform public health control strategies.This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with PCR-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. Eligible participants will be enrolled and randomized 1:1 to HCQ or ascorbic acid at the level of the household (all eligible participants in one household will receive the same intervention). Participants will be counseled about the preliminary in vitro data on HCQ activity against SARS CoV-2 and equipoise regarding efficacy in humans.The duration of study participation will be approximately 28 days.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• COVID-19
• Corona Virus Infection
• SARS (Severe Acute Respiratory Syndrome)
• SARS-CoV-2

Intervention

• Drug: Hydroxychloroquine Sulfate
  Eligible participants in a household randomized to this study arm will receive hydrochloroquine therapy
  Other Name: HCQ arm
• Drug: Ascorbic Acid
  Eligible participants in a household randomized to this study arm will receive ascorbic acid therapy.
  Other Name: Placebo arm

Study Arms

• Placebo Comparator: Ascorbic Acid
  Ascorbic acid 500 mg orally daily for 3 days, then 250 mg orally daily for 11 days
  Intervention: Drug: Ascorbic Acid
• Experimental: Hydroxychloroquine
  Hydrochloroquine 400 mg orally daily for 3 days, then 200 mg orally daily for an additional 11 days
  Intervention: Drug: Hydroxychloroquine Sulfate

Publications *

• Barnabas RV, Brown ER, Bershteyn A, Stankiewicz Karita HC, Johnston C, Thorpe LE, Kottkamp A, Neuzil KM, Laufer MK, Deming M, Paasche-Orlow MK, Kissinger PJ, Luk A, Paolino K, Landovitz RJ, Hoffman R, Schaafsma TT, Krows ML, Thomas KK, Morrison S, Haugen HS, Kidoguchi L, Wener M, Greninger AL, Huang ML, Jerome KR, Wald A, Celum C, Chu HY, Baeten JM; Hydroxychloroquine COVID-19 PEP Study Team. Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial. Ann Intern Med. 2021 Mar;174(3):344-352. doi: 10.7326/M20-6519. Epub 2020 Dec 8. Erratum In: Ann Intern Med. 2021 Mar;174(3):435.
• Barnabas RV, Brown E, Bershteyn A, Miller RS, Wener M, Celum C, Wald A, Chu H, Wesche D, Baeten JM; Hydroxychloroquine COVID-19 PEP Study Team. Efficacy of hydroxychloroquine for post-exposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults exposed to coronavirus disease (COVID-19): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 3;21(1):475. doi: 10.1186/s13063-020-04446-4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 14, 2021): 943
• Original Estimated Enrollment (submitted: March 29, 2020): 2000
• Actual Study Completion Date: October 8, 2020
• Actual Primary Completion Date: September 24, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men or women 18 to 80 years of age inclusive, at the time of signing the informed consent
• Willing and able to provide informed consent

• Had a close contact of a person (index) with known PCR-confirmed SARS-CoV-2 infection or who is currently being assessed for COVID-19. Close contact defined as:

  1. Household contact (i.e., residing with the index case in the 14 days prior to index diagnosis)
  2. Medical staff, first responders, or other care persons who cared for the index case without personal protection (mask and gloves)
• Less than 4 days since last exposure (close contact with a person with SARS-CoV-2 infection) to the index case
• Body weight < 100 kg (self-reported)
• Access to device and internet for Telehealth visits

Exclusion Criteria:

• Known hypersensitivity to HCQ or other 4-aminoquinoline compounds
• Currently hospitalized
• Symptomatic with subjective fever, cough, or sore throat
• Current medications exclude concomitant use of HCQ
• Concomitant use of other anti-malarial treatment or chemoprophylaxis
• History of retinopathy of any etiology
• Psoriasis
• Porphyria
• Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes < 1500) or thrombocytopenia (< 100 K)
• Concomitant use of digoxin, cyclosporin, cimetidine, or tamoxifen
• Known liver disease
• Known long QT syndrome
• Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study drugs, or planned use during the study period

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04328961
• Other Study ID Numbers: STUDY00009750; INV-016204 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified data from the study will be made available in accordance with the funder's open access policy.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Analytic Code
• Time Frame: Within 3 months of publication of primary results.
• Access Criteria: De-identified data from the study will be made available in accordance with the funder's open access policy.
• URL: https://www.gatesfoundation.org/how-we-work/general-information/open-access-policy

• Current Responsible Party: Ruanne Barnabas, University of Washington
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Washington
• Original Study Sponsor: Same as current
• Collaborators: Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Ruanne V. Barnabas, MBChB, DPhil; University of Washington

• PRS Account: University of Washington
• Verification Date: December 2021