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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT04328961
• Collaborator: Bill and Melinda Gates Foundation (Other)
• Enrollment: 943
• Locations: 8
• Arms: 2
• Actual Duration (Months): 6.3
• Patients Per Site: 117.9
• Patients Per Site Per Month: 18.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
COVID-19; Corona Virus Infection; SARS (Severe Acute Respiratory Syndrome); SARS-CoV-2	Drug: Hydroxychloroquine Sulfate; Drug: Ascorbic Acid	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 943 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Mar 31, 2020
• Actual Primary Completion Date: Sep 24, 2020
• Actual Study Completion Date: Oct 8, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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 Outcome Measures

1. 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

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles	Los Angeles	California	United States	90095
2	Tulane	New Orleans	Louisiana	United States	70118
3	University of Maryland, Baltimore	Baltimore	Maryland	United States	21201
4	Boston University	Boston	Massachusetts	United States	02215
5	NYU Langone Health	New York	New York	United States	10016
6	SUNY Upstate Medical University	Syracuse	New York	United States	13210
7	University of Washington, Coordinating Center	Seattle	Washington	United States	98104
8	UW Virology Research Clinic	Seattle	Washington	United States	98104

Sponsors and Collaborators

• University of Washington
• Bill and Melinda Gates Foundation

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Apr 9, 2020
• Statistical Analysis Plan - Aug 22, 2020

More Information

Publications

None provided.

• Responsible Party: Ruanne Barnabas, Associate Professor, School of Medicine: Global Health, University of Washington
• ClinicalTrials.gov Identifier: NCT04328961
• Other Study ID Numbers: STUDY00009750; INV-016204
• First Posted: Apr 1, 2020
• Last Update Posted: Dec 16, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Ruanne Barnabas, Associate Professor, School of Medicine: Global Health, University of Washington: novel coronavirus; post-exposure prophylaxis
• Additional relevant MeSH terms: Infections; COVID-19; Severe Acute Respiratory Syndrome; Coronavirus Infections; Syndrome; Ascorbic Acid; Hydroxychloroquine

Study Results

Participant Flow

Pre-assignment Detail	949 participants were assessed for eligibility, 114 were excluded and 829 were randomized.

Arm/Group Title	Ascorbic Acid	Hydroxychloroquine
Arm/Group Description	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.	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
Period Title: Overall Study
STARTED	422	407
COMPLETED	336	353
NOT COMPLETED	86	54

Baseline Characteristics

Arm/Group Title	Ascorbic Acid	Hydroxychloroquine	Total
Arm/Group Description	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.	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	Total of all reporting groups
Overall Participants	336	353	689
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	307 91.4%	322 91.2%	629 91.3%
>=65 years	29 8.6%	31 8.8%	60 8.7%
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	38	40	39
Sex: Female, Male (Count of Participants)
Female	197 58.6%	215 60.9%	412 59.8%
Male	139 41.4%	138 39.1%	277 40.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	86 25.6%	69 19.5%	155 22.5%
Not Hispanic or Latino	250 74.4%	284 80.5%	534 77.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	5 1.5%	7 2%	12 1.7%
Asian	43 12.8%	30 8.5%	73 10.6%
Native Hawaiian or Other Pacific Islander	1 0.3%	1 0.3%	2 0.3%
Black or African American	34 10.1%	20 5.7%	54 7.8%
White	160 47.6%	209 59.2%	369 53.6%
More than one race	86 25.6%	69 19.5%	155 22.5%
Unknown or Not Reported	7 2.1%	17 4.8%	24 3.5%
Region of Enrollment (participants) [Number]
United States	336 100%	353 100%	689 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Had Polymerase Chain Reaction (PCR) Confirmed SARS-CoV-2 Infection
Description	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

Outcome Measure Data

Analysis Population Description

The above participants qualified for the Modified Intention-to-Treat Cohort

Arm/Group Title	Ascorbic Acid	Hydroxychloroquine
Arm/Group Description	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.	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
Measure Participants	336	353
Count of Participants [Participants]	45 13.4%	53 15%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ascorbic Acid	Hydroxychloroquine
Arm/Group Description	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.	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
Measure Participants	336	353
Count of Participants [Participants]	48 14.3%	58 16.4%

3. Secondary Outcome

Title	Rate of Participant-reported Adverse Events
Description	Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults
Time Frame	28 days from start of Hydroxychloroquine therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ascorbic Acid	Hydroxychloroquine
Arm/Group Description	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.	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
Measure Participants	336	353
Count of Participants [Participants]	46 13.7%	66 18.7%

4. Secondary Outcome

Title	Number of Participants Who Had COVID-19 Disease
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ascorbic Acid	Hydroxychloroquine
Arm/Group Description	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.	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
Measure Participants	336	353
Count of Participants [Participants]	26 7.7%	37 10.5%

Adverse Events

Time Frame	Adverse event data was collected during the period of follow up, which was 28 days.
Adverse Event Reporting Description	Adverse event collection was obtained through daily surveys completed by participants. If participants were experiencing symptoms they were contacted by study staff for more information.
Arm/Group Title	Ascorbic Acid		Hydroxychloroquine
Arm/Group Description	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.		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
All Cause Mortality
	Ascorbic Acid		Hydroxychloroquine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/422 (0%)		0/407 (0%)
Serious Adverse Events
	Ascorbic Acid		Hydroxychloroquine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/422 (0.5%)		2/407 (0.5%)
Immune system disorders
Allergic Reaction	1/422 (0.2%)	1	1/407 (0.2%)	1
Infections and infestations
Hospitalizations	1/422 (0.2%)	1	1/407 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Ascorbic Acid		Hydroxychloroquine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/422 (10.9%)		66/407 (16.2%)
Ear and labyrinth disorders
Tinnitus	0/422 (0%)	0	0/407 (0%)	0
Eye disorders
Visual Changes	0/422 (0%)	0	4/407 (1%)	4
Gastrointestinal disorders
Diarrhea, abdominal discomfort, or vomiting	7/422 (1.7%)	7	25/407 (6.1%)	25
Nausea or upset stomach	10/422 (2.4%)	10	14/407 (3.4%)	14
General disorders
Neurologic reaction: irritability, dizziness, or vertifgo	11/422 (2.6%)	11	6/407 (1.5%)	6
Headache	7/422 (1.7%)	7	5/407 (1.2%)	5
Hot flashes, night sweats, or palpitations	6/422 (1.4%)	6	2/407 (0.5%)	2
Taste change or dry mouth	6/422 (1.4%)	6	1/407 (0.2%)	1
Fatigue	2/422 (0.5%)	2	4/407 (1%)	4
Immune system disorders
Allergic reaction	0/422 (0%)	0	2/407 (0.5%)	2
Skin and subcutaneous tissue disorders
Skin reaction/rash	8/422 (1.9%)	8	11/407 (2.7%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.