HERO-HCQ: Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine

• Sponsor: Adrian Hernandez (Other)
• Overall Status: Completed
• CT.gov ID: NCT04334148
• Collaborator: Patient-Centered Outcomes Research Institute (Other)
• Enrollment: 1,360
• Locations: 34
• Arms: 2
• Actual Duration (Months): 8.6
• Patients Per Site: 40
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

This is a double blind, placebo controlled study in approximately 2,000 health care workers at risk for being exposed to COVID-19. Eligible participants will be randomly assigned (1:1) to either treatment group (HCQ) or placebo in a double-blind fashion. Course of treatment is 30 days.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Hydroxychloroquine; Drug: Placebo oral tablet	Phase 3

Detailed Description

This is a double blind, placebo controlled study in approximately 2,000 health care workers at risk for being exposed to COVID-19. Eligible participants will be randomly assigned (1:1) to either treatment group (HCQ) or placebo in a double-blind fashion. After enrollment, baseline assessments will include nasopharyngeal swab for COVID-19 and a blood sample to detect seroconversion to COVID-19. For convenience, follow-up will be performed weekly through a direct to participant portal. A call center will provide support for any missed visits. Follow-up includes screening for any COVID-19 clinical infections, other respiratory infections, clinical events, adverse events, and Quality of Life (QoL) assessments. Course of treatment is 30 days. Participants are followed via survey weekly. At the end of treatment participants will return for repeat nasopharyngeal swab for COVID-19 and a blood sample to detect seroconversion to COVID-19. There will be one last contact at 8 weeks (2 months) from baseline.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double blind, placebo-controlled, randomized clinical trial.Double blind, placebo-controlled, randomized clinical trial.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Prevention
• Official Title: Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine Trial (HERO-HCQ Trial)
• Actual Study Start Date: Apr 22, 2020
• Actual Primary Completion Date: Dec 10, 2020
• Actual Study Completion Date: Jan 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Hydroxychloroquine Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30.	Drug: Hydroxychloroquine; oral self administered tablet; Other Names: Plaquenil
Placebo Comparator: Placebo Matching placebo tablets	Drug: Placebo oral tablet; oral self administered tablet

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Infection With COVID-19 Infection [30 days]

   This measure was a combination of confirmed infection and suspected infection. Confirmed clinical infection was defined as new-onset of fever or cough or dyspnea AND confirmed COVID-19 positive test result via local PCRI testing. Suspected infection was defined as new-onset fever or cough or dyspnea without local PCR testing due to local restrictions and/or testing policies.

Secondary Outcome Measures

1. Number of Participants With COVID-19 Viral Shedding [30 days]

   Number of participants with COVID-19 infection shedding via Covance swab PCR testing

2. Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs) [30 days]

   Safety and Tolerability as determined by subject reported serious adverse events (SAEs) and hydroxychloroquine-associated events of special interest. EOSIs include: arrhythmias (ventricular), hepatic failure, bone marrow failure, aplastic anemia, prolonged QT interval, angioedema, dermatitis exfoliative, acute generalized exanthematous pustulosis, psychosis, suicidal ideation, seizure, methemoglobinemia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion:

• Completed Informed Consent

• Age ≥ 18 years old

• Currently working in any environment in which there is a risk of exposure to patients with COVID-19 infections ("healthcare worker")

Exclusion Criteria:

• Prior diagnosis of COVID-19 infection

• Participation in another COVID-19 prophylaxis trial within 30 days of consent

• Respiratory illness with new-onset fever (Temperature > 100°F) or ongoing cough or dyspnea within 14 days

• Known allergy to HCQ or chloroquine

• Congenital prolonged QT syndrome

• Current or planned use of QT prolonging drugs (e.g. procainamide, disopyramide, mexiletine, flecainide, propafenone, amiodarone, sotalol, cimetidine, dronedarone, dofetilide, levofloxacin, ciprofloxacin, moxifloxacin) and other contraindicated medications

• End stage renal disease

• Pre-existing retinopathy

• Current or planned use of Hydroxychloroquine (study drug) for any indication

Current or planned use of the following for treatment or prevention of COVID-19 infection:

• Chloroquine

• Azithromycin

• Known cirrhosis or severe liver disease

• History of severe skin reactions such as Steven-Johnson syndrome, toxic epidermal necrolysis

• History of psoriasis or porphyria

• Ventricular arrhythmias requiring medical treatment

• Severe coronary artery disease or heart failure/cardiomyopathy with ongoing symptoms

• Current or planned use of use of anti-seizure drugs

• History of Glucose-6-phosphate dehydrogenase deficiency

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado/University of Colorado Denver	Aurora	Colorado	United States	80045
2	University of Florida	Gainesville	Florida	United States	32610
3	University of Florida Jacksonville	Jacksonville	Florida	United States	32206
4	University of Florida Health Central Florida	Leesburg	Florida	United States	34748
5	University of Miami Florida	Miami	Florida	United States	33136
6	Advent Health	Orlando	Florida	United States	32804
7	University of South Florida	Tampa	Florida	United States	33606
8	Northwestern Medicine	Chicago	Illinois	United States	60611
9	Rush University	Chicago	Illinois	United States	60612
10	University of Iowa	Iowa City	Iowa	United States	52242
11	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
12	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
13	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
14	Johns Hopkins	Baltimore	Maryland	United States	21287
15	University of Michigan	Ann Arbor	Michigan	United States	48109
16	Allina Health	Minneapolis	Minnesota	United States	55404
17	Mayo Clinic Hospital Rochester	Rochester	Minnesota	United States	55905
18	University of Missouri-Columbia	Columbia	Missouri	United States	65212
19	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
20	Hospital for Special Surgery	New York	New York	United States	10021
21	Columbia University, Irving Medical Center	New York	New York	United States	10032
22	Weill Cornell Medicine	New York	New York	United States	10065
23	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
24	Duke University Medical Center	Durham	North Carolina	United States	27710
25	Wake Forest Baptist Health Sciences	Winston-Salem	North Carolina	United States	27157
26	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
27	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
28	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania	United States	15213
29	Clinical Trials Center of Middle Tennessee	Franklin	Tennessee	United States	37067
30	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
31	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
32	Baylor Scott & White Medical Center-Temple	Temple	Texas	United States	76504
33	Seattle Children's Hospital	Seattle	Washington	United States	98105
34	Marshfield Clinic Health System	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• Adrian Hernandez
• Patient-Centered Outcomes Research Institute

Investigators

• Principal Investigator: Adrian Hernandez, MD, Duke University

Study Documents (Full-Text)

• Study Protocol - Jul 7, 2020
• Statistical Analysis Plan - Sep 4, 2020

More Information

Publications

None provided.

• Responsible Party: Adrian Hernandez, Professor of Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT04334148
• Other Study ID Numbers: Pro00105274
• First Posted: Apr 6, 2020
• Last Update Posted: Oct 12, 2021
• Last Verified: Oct 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 Adrian Hernandez, Professor of Medicine, Duke University: Hydroxychloroquine; Coronavirus Infections; Novel Coronavirus; Protective agents; Prophylaxis; Chemoprophylaxis; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome, Adult; Acute Lung Injury; Virus Diseases; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiratory Tract Infections; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Chloroquine; Chloroquine diphosphate
• Additional relevant MeSH terms: Hydroxychloroquine

Study Results

Participant Flow

Pre-assignment Detail	A participant was excluded from analysis population if they had a positive nasal swab test at baseline visit. This occurred to 1 participant assigned to the placebo group.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tablet	Matching placebo tablets Placebo oral tablet: oral self administered tablet
Period Title: Overall Study
STARTED	683	677
COMPLETED	683	676
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Hydroxychloroquine	Placebo	Total
Arm/Group Description	Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tablet	Matching placebo tablets Placebo oral tablet: oral self administered tablet	Total of all reporting groups
Overall Participants	683	676	1359
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.2 (11.9)	43.1 (11.2)	43.6 (11.6)
Sex: Female, Male (Count of Participants)
Female	442 64.7%	446 66%	888 65.3%
Male	241 35.3%	230 34%	471 34.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	39 5.7%	40 5.9%	79 5.8%
Not Hispanic or Latino	639 93.6%	629 93%	1268 93.3%
Unknown or Not Reported	5 0.7%	7 1%	12 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.1%	2 0.3%	3 0.2%
Asian	28 4.1%	27 4%	55 4%
Native Hawaiian or Other Pacific Islander	0 0%	2 0.3%	2 0.1%
Black or African American	18 2.6%	23 3.4%	41 3%
White	624 91.4%	610 90.2%	1234 90.8%
More than one race	6 0.9%	9 1.3%	15 1.1%
Unknown or Not Reported	6 0.9%	3 0.4%	9 0.7%
Region of Enrollment (participants) [Number]
United States	683 100%	676 100%	1359 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Infection With COVID-19 Infection
Description	This measure was a combination of confirmed infection and suspected infection. Confirmed clinical infection was defined as new-onset of fever or cough or dyspnea AND confirmed COVID-19 positive test result via local PCRI testing. Suspected infection was defined as new-onset fever or cough or dyspnea without local PCR testing due to local restrictions and/or testing policies.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tablet	Matching placebo tablets Placebo oral tablet: oral self administered tablet
Measure Participants	683	676
Count of Participants [Participants]	41 6%	53 7.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.200
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Number of Participants With COVID-19 Viral Shedding
Description	Number of participants with COVID-19 infection shedding via Covance swab PCR testing
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tablet	Matching placebo tablets Placebo oral tablet: oral self administered tablet
Measure Participants	683	676
Count of Participants [Participants]	2 0.3%	2 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Regression, Linear
	Comments

3. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs)
Description	Safety and Tolerability as determined by subject reported serious adverse events (SAEs) and hydroxychloroquine-associated events of special interest. EOSIs include: arrhythmias (ventricular), hepatic failure, bone marrow failure, aplastic anemia, prolonged QT interval, angioedema, dermatitis exfoliative, acute generalized exanthematous pustulosis, psychosis, suicidal ideation, seizure, methemoglobinemia.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Participants who completed the study.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tablet	Matching placebo tablets Placebo oral tablet: oral self administered tablet
Measure Participants	683	676
Count of Participants [Participants]	7 1%	8 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.802
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	60 days
Arm/Group Title	Hydroxychloroquine		Placebo
Arm/Group Description	Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tablet		Matching placebo tablets Placebo oral tablet: oral self administered tablet
All Cause Mortality
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/683 (0%)		0/677 (0%)
Serious Adverse Events
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/683 (0.4%)		2/677 (0.3%)
Cardiac disorders
Acute Myocardial Infarction	1/683 (0.1%)	1	0/677 (0%)	0
Hepatobiliary disorders
Haematuria	1/683 (0.1%)	1	0/677 (0%)	0
Infections and infestations
COVID-19	0/683 (0%)	0	1/677 (0.1%)	1
Psychiatric disorders
Anxiety	0/683 (0%)	0	1/677 (0.1%)	1
Suicide attempt	1/683 (0.1%)	1	0/677 (0%)	0
Alcohol Use Disorder	1/683 (0.1%)	1	0/677 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	0/683 (0%)	0	1/677 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/683 (0%)		0/677 (0%)

Limitations/Caveats

The study was underpowered to detect a small treatment effect. The trial was novel and improved feasibility, particularly during a pandemic. Testing was not performed at all institutions per local policies in HCW. These events were defined as suspected cases and were combined with the confirmed cases in the primary outcome. This resulted in few confirmed COVID-19 infections; thus, our primary outcome was primarily suspected COVID-19 clinical infection.

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.