Clinical trial NCT04328961: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Corona Virus Infection
SARS (Severe Acute Respiratory Syndrome)
SARS-CoV-2
Keywords: novel coronavirus
post-exposure prophylaxis
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2020-04-01
Enrollment: 943
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection
timeFrame: Day 1 through Day 14 after enrolment
measure: The Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection
timeFrame: Day 28 after enrolment
Secondary outcomes:
measure: Rate of Participant-reported Adverse Events
timeFrame: 28 days from start of Hydroxychloroquine therapy
measure: Number of Participants Who Had COVID-19 Disease
timeFrame: 28 days from enrolment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New Orleans
country: United States
facility: Tulane
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Seattle
country: United States
facility: University of Washington, Coordinating Center
state: Washington
city: Seattle
country: United States
facility: UW Virology Research Clinic
state: Washington
Study officials:
affiliation: University of Washington
name: Ruanne V. Barnabas, MBChB, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.