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)
1,360
Enrollment
34
Locations
2
Arms
8.6
Actual Duration (Months)
40
Patients Per Site
4.6
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Children's Hospital Colorado/University of Colorado DenverAuroraColoradoUnited States80045
    2University of FloridaGainesvilleFloridaUnited States32610
    3University of Florida JacksonvilleJacksonvilleFloridaUnited States32206
    4University of Florida Health Central FloridaLeesburgFloridaUnited States34748
    5University of Miami FloridaMiamiFloridaUnited States33136
    6Advent HealthOrlandoFloridaUnited States32804
    7University of South FloridaTampaFloridaUnited States33606
    8Northwestern MedicineChicagoIllinoisUnited States60611
    9Rush UniversityChicagoIllinoisUnited States60612
    10University of IowaIowa CityIowaUnited States52242
    11University of Kansas Medical CenterKansas CityKansasUnited States66160
    12University Medical Center New OrleansNew OrleansLouisianaUnited States70112
    13Ochsner Clinic FoundationNew OrleansLouisianaUnited States70121
    14Johns HopkinsBaltimoreMarylandUnited States21287
    15University of MichiganAnn ArborMichiganUnited States48109
    16Allina HealthMinneapolisMinnesotaUnited States55404
    17Mayo Clinic Hospital RochesterRochesterMinnesotaUnited States55905
    18University of Missouri-ColumbiaColumbiaMissouriUnited States65212
    19University of Nebraska Medical CenterOmahaNebraskaUnited States68198
    20Hospital for Special SurgeryNew YorkNew YorkUnited States10021
    21Columbia University, Irving Medical CenterNew YorkNew YorkUnited States10032
    22Weill Cornell MedicineNew YorkNew YorkUnited States10065
    23University of North Carolina at Chapel HillChapel HillNorth CarolinaUnited States27599
    24Duke University Medical CenterDurhamNorth CarolinaUnited States27710
    25Wake Forest Baptist Health SciencesWinston-SalemNorth CarolinaUnited States27157
    26The Ohio State University Wexner Medical CenterColumbusOhioUnited States43210
    27Temple University HospitalPhiladelphiaPennsylvaniaUnited States19140
    28University of Pittsburgh School of MedicinePittsburghPennsylvaniaUnited States15213
    29Clinical Trials Center of Middle TennesseeFranklinTennesseeUnited States37067
    30Vanderbilt University Medical CenterNashvilleTennesseeUnited States37232
    31University of Texas Southwestern Medical CenterDallasTexasUnited States75390
    32Baylor Scott & White Medical Center-TempleTempleTexasUnited States76504
    33Seattle Children's HospitalSeattleWashingtonUnited States98105
    34Marshfield Clinic Health SystemMarshfieldWisconsinUnited States54449

    Sponsors and Collaborators

    • Adrian Hernandez
    • Patient-Centered Outcomes Research Institute

    Investigators

    • Principal Investigator: Adrian Hernandez, MD, Duke University

    Study Documents (Full-Text)

    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

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailA 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 TitleHydroxychloroquinePlacebo
    Arm/Group DescriptionHydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tabletMatching placebo tablets Placebo oral tablet: oral self administered tablet
    Period Title: Overall Study
    STARTED683677
    COMPLETED683676
    NOT COMPLETED01

    Baseline Characteristics

    Arm/Group TitleHydroxychloroquinePlaceboTotal
    Arm/Group DescriptionHydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tabletMatching placebo tablets Placebo oral tablet: oral self administered tabletTotal of all reporting groups
    Overall Participants6836761359
    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
    TitleNumber of Participants With Clinical Infection With COVID-19 Infection
    DescriptionThis 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 Frame30 days

    Outcome Measure Data

    Analysis Population Description
    Participants who completed the study.
    Arm/Group TitleHydroxychloroquinePlacebo
    Arm/Group DescriptionHydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tabletMatching placebo tablets Placebo oral tablet: oral self administered tablet
    Measure Participants683676
    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 Hypothesisp-Value0.200
    Comments
    MethodFisher Exact
    Comments
    2. Secondary Outcome
    TitleNumber of Participants With COVID-19 Viral Shedding
    DescriptionNumber of participants with COVID-19 infection shedding via Covance swab PCR testing
    Time Frame30 days

    Outcome Measure Data

    Analysis Population Description
    Participants who completed the study.
    Arm/Group TitleHydroxychloroquinePlacebo
    Arm/Group DescriptionHydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tabletMatching placebo tablets Placebo oral tablet: oral self administered tablet
    Measure Participants683676
    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 Hypothesisp-Value1.0
    Comments
    MethodRegression, Linear
    Comments
    3. Secondary Outcome
    TitleNumber of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs)
    DescriptionSafety 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 Frame30 days

    Outcome Measure Data

    Analysis Population Description
    Participants who completed the study.
    Arm/Group TitleHydroxychloroquinePlacebo
    Arm/Group DescriptionHydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tabletMatching placebo tablets Placebo oral tablet: oral self administered tablet
    Measure Participants683676
    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 Hypothesisp-Value0.802
    Comments
    MethodChi-squared
    Comments

    Adverse Events

    Time Frame60 days
    Adverse Event Reporting Description
    Arm/Group TitleHydroxychloroquinePlacebo
    Arm/Group DescriptionHydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. Hydroxychloroquine: oral self administered tabletMatching placebo tablets Placebo oral tablet: oral self administered tablet
    All Cause Mortality
    HydroxychloroquinePlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/683 (0%) 0/677 (0%)
    Serious Adverse Events
    HydroxychloroquinePlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/683 (0.4%) 2/677 (0.3%)
    Cardiac disorders
    Acute Myocardial Infarction1/683 (0.1%) 10/677 (0%) 0
    Hepatobiliary disorders
    Haematuria1/683 (0.1%) 10/677 (0%) 0
    Infections and infestations
    COVID-190/683 (0%) 01/677 (0.1%) 1
    Psychiatric disorders
    Anxiety0/683 (0%) 01/677 (0.1%) 1
    Suicide attempt1/683 (0.1%) 10/677 (0%) 0
    Alcohol Use Disorder1/683 (0.1%) 10/677 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure0/683 (0%) 01/677 (0.1%) 1
    Other (Not Including Serious) Adverse Events
    HydroxychloroquinePlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/683 (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.

    Results Point of Contact

    Name/TitleDr. Susanna Naggie
    OrganizationDuke University
    Phone919-684-2584
    Emailsusanna.naggie@duke.edu
    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