Pre-exposure Prophylaxis for SARS-Coronavirus-2

Sponsor
University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT04328467
Collaborator
(none)
1,483
2
3
3.2
741.5
230.3

Study Details

Study Description

Brief Summary

Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The current standard of care is observation and quarantine after exposure to COVID-19. There is no approved treatment or prophylaxis for COVID-19.

As of March 6, 2020, the CDC estimates that the transmission of SARS-CoV2 after a U.S. household close contract is 10.5% (95%CI, 2.9 to 31.4%). Among all close contacts, the SARS-CoV2 transmission rate is estimated at 0.45% (95%CI, 0.12 to 1.6%) by the CDC. These estimates are based on monitoring of travel-associated COVID19 cases. Conversely, in a setting with community transmission, the secondary attack rate in China was 35% (95%CI, 27-44%) based on 48 transmissions among 137 persons in 9 index patients.

Chloroquine or Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or reduce disease severity. It is not known at what dosing hydroxychloroquine may be effective for pre-exposure prophylaxis.

Study Design

Study Type:
Interventional
Actual Enrollment :
1483 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
Actual Study Start Date :
Apr 6, 2020
Actual Primary Completion Date :
Jul 13, 2020
Actual Study Completion Date :
Jul 13, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intervention Once Weekly

400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks

Drug: Hydroxychloroquine
Hydroxychloroquine; 200mg tablet; oral
Other Names:
  • Plaquenil
  • Experimental: Intervention Twice Weekly

    400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks

    Drug: Hydroxychloroquine
    Hydroxychloroquine; 200mg tablet; oral
    Other Names:
  • Plaquenil
  • Placebo Comparator: Control Group

    Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks

    Other: Placebo
    Placebo; tablet; oral

    Outcome Measures

    Primary Outcome Measures

    1. COVID-19-free Survival [up to 12 weeks]

      Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment.

    Secondary Outcome Measures

    1. Number of Confirmed SARS-CoV-2 Detection [up to 12 weeks]

      Outcome reported as the number of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

    2. Incidence of Possible COVID-19 Symptoms [up to 12 weeks]

      Outcome reported as the count of participants in each arm who report COVID-19-related symptoms during study treatment.

    3. Incidence of All-cause Study Medicine Discontinuation [up to 12 weeks]

      Outcome reported as the count of participants in each arm who discontinue study medication use for any reason during treatment.

    4. Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End [up to 12 weeks]

      Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.

    5. Incidence of Hospitalization for COVID-19 or Death [up to 12 weeks]

      Outcome reported as the number of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

    6. Incidence of Possible Study Medication-related Side Effects [up to 12 weeks]

      Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • A healthcare worker at high risk for COVID-19 exposure (defined below):

    • Persons primarily working in emergency departments (physicians, nurses, ancillary staff, triage personnel)

    • Persons primarily working in intensive care units (physicians, nurses, ancillary staff, respiratory therapists)

    • Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse anesthetists (CRNAs)

    • First responders (i.e. EMTs, paramedics)

    Exclusion Criteria:
    • Active COVID-19 disease

    • Prior COVID-19 disease

    • Current fever, cough, shortness of breath

    • Allergy to chloroquine or hydroxychloroquine

    • Prior retinal eye disease

    • Known Chronic Kidney disease, Stage 4 or 5 or dialysis

    • Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency

    • Weight <40 kg

    • Prolonged QT syndrome

    • Current use of hydroxychloroquine, chloroquine, or cardiac medicines of flecainide, amiodarone, digoxin, procainamide, or propafenone

    • Current use of medications with known significant drug-drug interactions: artemether, lumefantrine, mefloquine, tamoxifen, or methotrexate.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Nationwide Enrollment via Internet, please email: covid19@umn.edu Minneapolis Minnesota United States 55455
    2 University of Minnesota Minneapolis Minnesota United States 55455

    Sponsors and Collaborators

    • University of Minnesota

    Investigators

    • Principal Investigator: Radha Rajasingham, MD, University of Minnesota

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT04328467
    Other Study ID Numbers:
    • MED-2020-28720
    First Posted:
    Mar 31, 2020
    Last Update Posted:
    Jul 2, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Period Title: Overall Study
    STARTED 494 495 494
    COMPLETED 490 493 493
    NOT COMPLETED 4 2 1

    Baseline Characteristics

    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group Total
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral Total of all reporting groups
    Overall Participants 494 495 494 1483
    Age (years) [Mean (Inter-Quartile Range) ]
    Mean (Inter-Quartile Range) [years]
    42
    41
    40
    41
    Sex: Female, Male (Count of Participants)
    Female
    261
    52.8%
    258
    52.1%
    241
    48.8%
    760
    51.2%
    Male
    233
    47.2%
    237
    47.9%
    253
    51.2%
    723
    48.8%
    Race/Ethnicity, Customized (Count of Participants)
    White or Caucasian
    431
    87.2%
    421
    85.1%
    419
    84.8%
    1271
    85.7%
    Black of African
    5
    1%
    5
    1%
    10
    2%
    20
    1.3%
    Asian
    23
    4.7%
    23
    4.6%
    29
    5.9%
    75
    5.1%
    Native Hawaiian or Pacific Islander
    0
    0%
    1
    0.2%
    1
    0.2%
    2
    0.1%
    Hispanic or Latino
    18
    3.6%
    22
    4.4%
    18
    3.6%
    58
    3.9%
    Native American or Alaska Native
    4
    0.8%
    7
    1.4%
    8
    1.6%
    19
    1.3%
    Middle Eastern
    6
    1.2%
    5
    1%
    4
    0.8%
    15
    1%
    South Asian
    17
    3.4%
    18
    3.6%
    12
    2.4%
    47
    3.2%
    Other
    3
    0.6%
    1
    0.2%
    4
    0.8%
    8
    0.5%
    Region of Enrollment (participants) [Number]
    United States
    493
    99.8%
    494
    99.8%
    493
    99.8%
    1480
    99.8%
    Canada
    1
    0.2%
    1
    0.2%
    1
    0.2%
    3
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title COVID-19-free Survival
    Description Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 494 495 494
    Count of Participants [Participants]
    464
    93.9%
    468
    94.5%
    454
    91.9%
    2. Secondary Outcome
    Title Number of Confirmed SARS-CoV-2 Detection
    Description Outcome reported as the number of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 494 495 494
    Count of Participants [Participants]
    29
    5.9%
    29
    5.9%
    39
    7.9%
    3. Secondary Outcome
    Title Incidence of Possible COVID-19 Symptoms
    Description Outcome reported as the count of participants in each arm who report COVID-19-related symptoms during study treatment.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 494 495 494
    Count of Participants [Participants]
    29
    5.9%
    28
    5.7%
    38
    7.7%
    4. Secondary Outcome
    Title Incidence of All-cause Study Medicine Discontinuation
    Description Outcome reported as the count of participants in each arm who discontinue study medication use for any reason during treatment.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 494 495 494
    Count of Participants [Participants]
    119
    24.1%
    158
    31.9%
    133
    26.9%
    5. Secondary Outcome
    Title Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End
    Description Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Measure was only collected for one participant in the twice-weekly intervention group and one participant in the control group. No participants in the once-weekly intervention group were sampled for this measure.
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 0 1 1
    Mean (Standard Deviation) [score on a scale]
    1
    (NA)
    1
    (NA)
    6. Secondary Outcome
    Title Incidence of Hospitalization for COVID-19 or Death
    Description Outcome reported as the number of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 494 495 494
    Count of Participants [Participants]
    3
    0.6%
    8
    1.6%
    9
    1.8%
    7. Secondary Outcome
    Title Incidence of Possible Study Medication-related Side Effects
    Description Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    Measure Participants 494 495 494
    Count of Participants [Participants]
    148
    30%
    168
    33.9%
    100
    20.2%

    Adverse Events

    Time Frame up to 12 weeks
    Adverse Event Reporting Description
    Arm/Group Title Intervention Once Weekly Intervention Twice Weekly Control Group
    Arm/Group Description 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Placebo: Placebo; tablet; oral
    All Cause Mortality
    Intervention Once Weekly Intervention Twice Weekly Control Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/494 (0%) 0/495 (0%) 0/494 (0%)
    Serious Adverse Events
    Intervention Once Weekly Intervention Twice Weekly Control Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/494 (0.6%) 6/495 (1.2%) 8/494 (1.6%)
    Cardiac disorders
    Chest Pain 0/494 (0%) 0 0/495 (0%) 0 2/494 (0.4%) 2
    Heart Palpitations 0/494 (0%) 0 0/495 (0%) 0 2/494 (0.4%) 2
    Tachycardia 0/494 (0%) 0 0/495 (0%) 0 1/494 (0.2%) 1
    Atrial Fibrillation 0/494 (0%) 0 0/495 (0%) 0 2/494 (0.4%) 2
    Endocrine disorders
    Hyperthyroid 0/494 (0%) 0 0/495 (0%) 0 1/494 (0.2%) 1
    Gastrointestinal disorders
    Diverticulitis 1/494 (0.2%) 1 0/495 (0%) 0 0/494 (0%) 0
    General disorders
    Other Not Specified 0/494 (0%) 0 2/495 (0.4%) 2 0/494 (0%) 0
    Injury, poisoning and procedural complications
    Motor Vehicle Accident 0/494 (0%) 0 1/495 (0.2%) 1 0/494 (0%) 0
    Renal and urinary disorders
    Urinary Tract Infection 0/494 (0%) 0 1/495 (0.2%) 1 1/494 (0.2%) 1
    Surgical and medical procedures
    Hysteroscopy 1/494 (0.2%) 1 0/495 (0%) 0 0/494 (0%) 0
    Spinal Surgery 1/494 (0.2%) 1 0/495 (0%) 0 0/494 (0%) 0
    Elective Coronary Angiogram 0/494 (0%) 0 1/495 (0.2%) 1 0/494 (0%) 0
    Gall Bladder Surgery 0/494 (0%) 0 1/495 (0.2%) 1 0/494 (0%) 0
    Sarcoidosis Biopsy 0/494 (0%) 0 0/495 (0%) 0 1/494 (0.2%) 1
    Other (Not Including Serious) Adverse Events
    Intervention Once Weekly Intervention Twice Weekly Control Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/494 (0%) 0/495 (0%) 0/494 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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/Title Radha Rajasingham, MD
    Organization University of Minnesota
    Phone 612-626-8171
    Email radha@umn.edu
    Responsible Party:
    University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT04328467
    Other Study ID Numbers:
    • MED-2020-28720
    First Posted:
    Mar 31, 2020
    Last Update Posted:
    Jul 2, 2021
    Last Verified:
    Jun 1, 2021