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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Hydroxychloroquine Sulfate
* Drug: Ascorbic Acid


Participation Criteria
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Eligibility Criteria
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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: Household contact (i.e., residing with the index case in the 14 days prior to index diagnosis) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Ascorbic Acid<br>Ascorbic acid 500 mg orally daily for 3 days, then 250 mg orally daily for 11 days | Drug: Ascorbic Acid<br>* Eligible participants in a household randomized to this study arm will receive ascorbic acid therapy.<br>* Other names: Placebo arm;|
| Experimental: Hydroxychloroquine<br>Hydrochloroquine 400 mg orally daily for 3 days, then 200 mg orally daily for an additional 11 days | Drug: Hydroxychloroquine Sulfate<br>* Eligible participants in a household randomized to this study arm will receive hydrochloroquine therapy<br>* Other names: HCQ arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | 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 | Day 1 through Day 14 after enrolment | 
| The Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit | Day 28 after enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Participant-reported Adverse Events | Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults | 28 days from start of Hydroxychloroquine therapy | 
| Number of Participants Who Had COVID-19 Disease | 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. | 28 days from enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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novel coronavirus, post-exposure prophylaxis