Corona Virus Infection, COVID-19, SARS-CoV-2, SARS (Severe Acute Respiratory Syndrome)
Conditions
Keywords
novel coronavirus, post-exposure prophylaxis
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.
Interventions
DRUGHydroxychloroquine Sulfate
Eligible participants in a household randomized to this study arm will receive hydrochloroquine therapy
DRUGAscorbic Acid
Eligible participants in a household randomized to this study arm will receive ascorbic acid therapy.
Sponsors
Bill and Melinda Gates Foundation
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | 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 | Day 28 after enrolment | Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Participant-reported Adverse Events | 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 | 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. |
Countries
United States
Participant flow
Pre-assignment details
949 participants were assessed for eligibility, 114 were excluded and 829 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Ascorbic Acid Ascorbic acid 500 mg orally daily for 3 days, then 250 mg orally daily for 11 days
Ascorbic Acid: Eligible participants in a household randomized to this study arm will receive ascorbic acid therapy. | 336 |
| Hydroxychloroquine Hydrochloroquine 400 mg orally daily for 3 days, then 200 mg orally daily for an additional 11 days
Hydroxychloroquine Sulfate: Eligible participants in a household randomized to this study arm will receive hydrochloroquine therapy | 353 |
| Total | 689 |
Baseline characteristics
| Characteristic | Ascorbic Acid | Hydroxychloroquine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 31 Participants | 60 Participants |
| Age, Categorical Between 18 and 65 years | 307 Participants | 322 Participants | 629 Participants |
| Age, Continuous | 38 Years | 40 Years | 39 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 86 Participants | 69 Participants | 155 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 250 Participants | 284 Participants | 534 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) Asian | 43 Participants | 30 Participants | 73 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 20 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 86 Participants | 69 Participants | 155 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 17 Participants | 24 Participants |
| Race (NIH/OMB) White | 160 Participants | 209 Participants | 369 Participants |
| Region of Enrollment United States | 336 participants | 353 participants | 689 participants |
| Sex: Female, Male Female | 197 Participants | 215 Participants | 412 Participants |
| Sex: Female, Male Male | 139 Participants | 138 Participants | 277 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 422 | 0 / 407 |
| other Total, other adverse events | 46 / 422 | 66 / 407 |
| serious Total, serious adverse events | 2 / 422 | 2 / 407 |
Outcome results
Primary
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
Time frame: Day 1 through Day 14 after enrolment
Population: The above participants qualified for the Modified Intention-to-Treat Cohort
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ascorbic Acid | Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | 45 Participants |
| Hydroxychloroquine | Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | 53 Participants |
Primary
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
Time frame: Day 28 after enrolment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ascorbic Acid | The Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | 48 Participants |
| Hydroxychloroquine | The Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection | 58 Participants |
Secondary
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.
Time frame: 28 days from enrolment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ascorbic Acid | Number of Participants Who Had COVID-19 Disease | 26 Participants |
| Hydroxychloroquine | Number of Participants Who Had COVID-19 Disease | 37 Participants |
Secondary
Rate of Participant-reported Adverse Events
Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults
Time frame: 28 days from start of Hydroxychloroquine therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ascorbic Acid | Rate of Participant-reported Adverse Events | 46 Participants |
| Hydroxychloroquine | Rate of Participant-reported Adverse Events | 66 Participants |