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Will Hydroxychloroquine Impede or Prevent COVID-19 (WHIP COVID-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04341441
Recruitment Status : Recruiting
First Posted : April 10, 2020
Last Update Posted : May 7, 2020
Sponsor:
Information provided by (Responsible Party):
William W. O'Neill, Henry Ford Health System

Brief Summary:

This is a prospective, multi-site study designed to evaluate whether the use of hydroxychloroquine in healthcare workers (HCW), Nursing Home Workers (NHW), first responders (FR), and Detroit Department of Transportation bus drivers (DDOT) in SE, Michigan, can prevent the acquisition, symptoms and clinical COVID-19 infection

The primary objective of this study is to determine whether the use of daily or weekly oral hydroxychloroquine (HCQ) therapy will prevent SARS-CoV-2 infection and COVID-19 viremia and clinical COVID-19 infection healthcare workers (HCW) and first responders (FR) (EMS, Fire, Police, bus drivers) in Southeast Michigan.

Preventing COVID-19 transmission to HCW, FR, and Detroit Department of Transportation (DDOT) bus drivers is a critical step in preserving the health care and first responder force, the prevention of COVID-19 transmission in health care facilities, with the potential to preserve thousands of lives in addition to sustaining health care systems and civil services both nationally and globally. If efficacious, further studies on the use of hydroxychloroquine to prevent COVID-19 in the general population could be undertaken, with a potential impact on hundreds of thousands of lives.


Condition or disease Intervention/treatment Phase
COVID-19 Coronavirus Coronavirus Infections SARS-CoV 2 Drug: Hydroxychloroquine - Daily Dosing Drug: Hydroxychloroquine - Weekly Dosing Other: Placebo oral tablet Diagnostic Test: Monitoring Visit - Baseline Diagnostic Test: Monitoring Visit - Week 4 Diagnostic Test: Monitoring Visit - Week 8 Other: Weekly Assessment Phase 3

Detailed Description:

The study will randomize a total of 3,000 HCW, NHW, FR and DDOT bus drivers within Henry Ford Hospital System, the Detroit COVID Consortium in Southeast, Michigan. The participants will be randomized in a 1:1:1 blinded comparison of daily HCQ, weekly HCQ, or placebo. A fourth non-randomized comparator group of HCW, NHW, DDOT bus drivers, and FR who are currently on standard HCQ therapy will be recruited to assess the impact of weightbased daily dosing of HCQ as compared to the randomized arms.

Eligible participants who are asymptomatic for pre-specified signs and symptoms suggestive of COVID-19 infection will have a whole blood specimen obtained at study entry.

Participants will be provided with weekly dosing of hydroxychloroquine (HCQ) 400mg po q weekly, daily dosing of HCQ 200mg po q daily following a loading dose of 400mg day 1, or placebo. Participants will receive monitoring at each study week visit to assess for the development of COVID-19 related symptoms, COVID-19 clinical disease, and medication side effects. At week 8 or if diagnosed positive, participants will provide additional samples of whole blood and complete the final study questionnaire.

Data including demographic, clinical results, work duties, location of main work area and possible exposures in the community will be collected through questionnaires and EMR review. Disease-specific, immunologic, and other serologic marker data will be obtained from stored samples.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a prospective, multi-site study designed to evaluate whether the use of hydroxychloroquine in healthcare workers (HCW) and first responders (FR) in southeast (SE) Michigan, can prevent the acquisition, symptoms and clinical COVID-19 infection.

The study will randomize a total of 3,000 Healthcare Workers and First Responders, age ≥18 years or older, through the Henry Ford Health System, Detroit COVID Consortium. The participants who meeting study entry criteria and are not on HCQ prior to study enrollment will be randomized in a 1:1:1 blinded comparison of daily or weekly oral hydroxychloroquine versus oral placebo for 8 weeks.

A fourth non-randomized comparator group will be enrolled in the study comprising of HCW who are chronically on HCQ as part of their standard of care for their autoimmune disease(s). This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Blinded randomization will be performed by the Henry Ford Hospital Public Health Sciences investigators once the participants are determined to be eligible for enrollment. Randomization will be stratified by study site and risk of exposure based on location of work and type of work.

Once enrolled, each Participant will be assigned a unique identifier (detailed in the full protocol). This number, along with the assigned site number, will constitute the Subject Identifier (Subject ID).

Primary Purpose: Prevention
Official Title: Will Hydroxychloroquine Impede or Prevent COVID-19: WHIP COVID-19 Study
Actual Study Start Date : April 7, 2020
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : April 30, 2021


Arm Intervention/treatment
Active Comparator: Study Drug - Daily Dose
The daily hydroxychloroquine treatment arm will receive a 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care.
Drug: Hydroxychloroquine - Daily Dosing

The daily hydroxychloroquine treatment arm will receive a 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care.

All treatment groups will receive placebo pills to have the patients take 2 pills a day.

Other Names:
  • Study Drug - Daily
  • Daily Oral Dosing

Diagnostic Test: Monitoring Visit - Baseline
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Baseline Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 4
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 4 - Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 8
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 8 - Monitoring Visit

Other: Weekly Assessment
Participants will be asked to contact the study team if COVID-19 infection is established at any time during the study. For study weeks 1,2,3,5,6 &7, Participants will receive a monitoring questionnaire to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects. These monitoring visits will be done by telephone and/or electronic encounters (virtual visits, email), whichever method the patient prefers to encourage adherence to the monitoring.
Other Name: Monitoring Call

Active Comparator: Study Drug - Weekly Dose
The once weekly randomized treatment arm will receive the proposed dose of hydroxychloroquine for prophylaxis of malaria is 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria.
Drug: Hydroxychloroquine - Weekly Dosing

The once weekly randomized treatment arm will receive the proposed dose of hydroxychloroquine for prophylaxis of malaria is 6.5 mg/kg per dose (maximum of 400 mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria

All treatment groups will receive placebo pills to have the patients take 2 pills a day.

Other Name: Weekly Oral Dosing

Diagnostic Test: Monitoring Visit - Baseline
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Baseline Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 4
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 4 - Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 8
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 8 - Monitoring Visit

Other: Weekly Assessment
Participants will be asked to contact the study team if COVID-19 infection is established at any time during the study. For study weeks 1,2,3,5,6 &7, Participants will receive a monitoring questionnaire to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects. These monitoring visits will be done by telephone and/or electronic encounters (virtual visits, email), whichever method the patient prefers to encourage adherence to the monitoring.
Other Name: Monitoring Call

Active Comparator: Placebo
All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.
Other: Placebo oral tablet

Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day..

Participants will receive a monitoring phone call at 4 weeks post study entry to monitor for COVID-19 symptoms and medication side effects. At week 8, participants will provide additional samples of whole blood.

Additional studies will include serology, inflammatory and other disease associated markers. Clinical data and location of main work area will be collected.

Other Name: Placebo

Diagnostic Test: Monitoring Visit - Baseline
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Baseline Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 4
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 4 - Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 8
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 8 - Monitoring Visit

Other: Weekly Assessment
Participants will be asked to contact the study team if COVID-19 infection is established at any time during the study. For study weeks 1,2,3,5,6 &7, Participants will receive a monitoring questionnaire to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects. These monitoring visits will be done by telephone and/or electronic encounters (virtual visits, email), whichever method the patient prefers to encourage adherence to the monitoring.
Other Name: Monitoring Call

Active Comparator: Non-Randomized Active Comparator
A non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s). This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy.
Diagnostic Test: Monitoring Visit - Baseline
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Baseline Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 4
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 4 - Monitoring Visit

Diagnostic Test: Monitoring Visit - Week 8
Face-to-face monitoring visit to obtain monitoring questionnaires to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects, and collect study blood samples. Three (3) blood specimens will be collected from each Participant using the sterile procedure as routine standard of care. A total of five (5) 10 mL tubes of whole blood will be collected at each timepoint.
Other Name: Week 8 - Monitoring Visit

Other: Weekly Assessment
Participants will be asked to contact the study team if COVID-19 infection is established at any time during the study. For study weeks 1,2,3,5,6 &7, Participants will receive a monitoring questionnaire to assess for COVID-19 symptoms/diagnosis, adherence and medication side effects. These monitoring visits will be done by telephone and/or electronic encounters (virtual visits, email), whichever method the patient prefers to encourage adherence to the monitoring.
Other Name: Monitoring Call




Primary Outcome Measures :
  1. To determine if the use of hydroxychloroquine as preventive therapy decreases the rate of acquisition of SARS-CoV 2 infections and clinical COVID-19 disease in Study Participants for each randomized treatment arm as compared to placebo. [ Time Frame: 8 Weeks ]
    We will measure the difference in new cases of COVID-19 disease between randomized treatment arms. Plan statistical analyses will include the assumption that up 10% of HCW at risk will become infected if no prophylactic treatment is provided. Therefore we expect that HCQ treatment arm will provide a reduction in the number of SARS-CoV 2 infections by 30%, with an expected study retention rate of 90%, a sample size of ~1500 participants per group, will have an 80% power to detect the difference at p=0.05.


Secondary Outcome Measures :
  1. Determine the effect of hydroxychloroquine dose in the prevention of COVID-19 viremia and disease. [ Time Frame: 8 Weeks ]
    Compare the rates of SARS-CoV 2 infections between the randomized treatment arms and the control arms to determine the effect of HCQ dose in the prevention of COVID-19 viremia and disease as determined by study visits, weekly questionnaires, and blood samples.

  2. Assess the impact of chronic weight-based dosing of HCQ for COVID-19 prevention. [ Time Frame: 8 Weeks ]
    Comparison of the rates of SARS-CoV 2 infections in the non-randomized comparator arm to the randomized groups to assess the impact of chronic weight-based dosing of HCQ for COVID-19 prevention via weekly questionnaire and/or blood samples.

  3. Comparison of the rate of SARS-CoV 2 infections as measured by IgM/IgG seroconversion in study participants receiving randomized HCQ versus placebo. [ Time Frame: 8 Weeks ]
    Measurement of the rate of SARS-CoV 2 infections as measured by IgM/IgG seroconversion in study participants receiving randomized HCQ versus placebo via blood samples.

  4. Compare the seroprevalence of SARS-CoV 2 IgM/IgG positive samples at study entry and study conclusion in all participants receiving HCQ compared to those receiving placebo. [ Time Frame: 8 Weeks ]
    Measurement of the seroprevalence of SARS-CoV 2 IgM/IgG positive samples at study entry and study conclusion in all participants receiving HCQ compared to those receiving placebo via blood samples.

  5. Comparison of the emergence of clinical symptoms or COVID-19 diagnosis in participants presenting asymptomatically at study entry but identified as seropositive by serology at entry between the randomized treatment arms and comparator arm. [ Time Frame: 8 Weeks ]
    Measurement of the emergence of clinical symptoms or COVID-19 diagnosis in participants presenting asymptomatically at study entry but identified as seropositive by serology at entry between the randomized treatment arms and comparator arm and via weekly questionnaire and/or blood samples.

  6. To examine the level of care needed by participants in each arm developing COVID19 as measured as requiring emergency room visit, hospitalization or able to stay home without hospital care. [ Time Frame: 8 Weeks ]
    Review of the level of care needed by participants in each arm developing COVID19 as measured as requiring emergency room visit, hospitalization or able to stay home without hospital care via weekly questionnaire.

  7. Determine the safety and tolerability of HCQ dosing for preventive strategy against COVID-19 as measured by adverse events and serious adverse events. [ Time Frame: 8 Weeks ]
    Measurement of the safety and tolerability of HCQ dosing for preventive strategy against COVID-19 as measured by adverse events and serious adverse events reported via weekly questionnaire.

  8. To examine other clinical determinants contributing to the risk of SARS-CoV 2 infection in healthcare workers and first responders. [ Time Frame: 8 Weeks ]
    Examination of other clinical determinants contributing to the risk of SARS-CoV 2 infection including demographics, work type and location, positive COVID-19 partners, possible exposures and clinical symptoms via study visits and weekly questionnaire.

  9. Examine the association between HCQ drug levels and development of COVID-19 symptoms or positive test results. [ Time Frame: 8 Weeks ]
    Examine the association between HCQ drug levels and development of COVID-19 symptoms or positive test results via weekly questionnaire and/or blood samples.

  10. identify immunologic, serological and inflammatory markers associated with acquisition and response to COVID-19 in both HCQ and placebo Participants developing laboratory or clinical confirmed disease. [ Time Frame: 8 weeks ]
    Identification of immunologic, serological and inflammatory markers associated with acquisition and response to COVID-19 in both HCQ and placebo Participants developing laboratory or clinical confirmed disease via study visits, weekly questionnaire, and blood samples.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Participant is willing and able to provide informed consent.
  2. Participant is 18-75 years of age.
  3. Participant does not have symptoms of respiratory infection, including cough, fevers (temperature >38.0C), difficulty breathing, shortness of breath, chest pains, malaise, myalgia, headaches, nausea or vomiting, or other symptoms associated with COVID-19.
  4. Participant is willing to provide blood samples for the study.
  5. Subject agrees to all aspects of the study.
  6. The participant has no known allergies or contraindications (as stated in the consent form) to the use of hydroxychloroquine (HCQ) as noted in the exclusion criteria and Pharmacy sections.

Exclusion Criteria:

  1. Does not meet inclusion criteria.
  2. Participant unable or unwilling to provide informed consent.
  3. Participant has any of the symptoms above or screens positive for possible COVID-19 disease.
  4. Participant is currently enrolled in a study to evaluate an investigational drug.
  5. Vulnerable populations deemed inappropriate for study by the site Principal Investigator.
  6. The participant has a known allergy/hypersensitivity or has a medication or co-morbidity (including history of gastric bypass, epilepsy, cardiovascular disease or renal failure) that prevents the use of HCQ (see pharmacy section).
  7. The participant is a woman of childbearing age whose pregnancy status is unknown and is not willing to use 2 methods of contraception.
  8. The participant is pregnant or nursing.
  9. The participant was diagnosed with retinopathy prior to study entry.
  10. The participant has a diagnosis of porphyria prior to study entry.
  11. The participant has renal failure with a creatinine clearance of <10 ml/min, pre-dialysis or requiring dialysis.
  12. The Participant has a family history of Sudden Cardiac Death.
  13. The participant is currently on diuretic therapy.
  14. The participant has a history of known Prolonged QT Syndrome.
  15. The participant is already taking any of the following medications: Abiraterone acetate, Agalsidase, Amodiaquine, Azithromycin, Conivaptan, Dabrafenib, Dacomitinib, Dapsone (Systemic), Digoxin, Enzalutamide, Fusidic Acid (Systemic), Idelalisib, Lanthanum, Lumefantrine, Mefloquine, Mifepristone, Mitotane, Pimozide, QT-prolonging Agents, Stiripentol).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04341441


Contacts
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Contact: Dee Dee Wang, MD 313-574-2651 whipcovid19@hfhs.org
Contact: Laurie Nightengale, MD 313-574-2651 whipcovid19@hfhs.org

Locations
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United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Dee Dee Wang, MD    313-574-2651    whipcovid19@hfhs.org   
Contact: John McKinnon, MD    313-574-2651    whipcovid19@hfhs.org   
Detroit Department of Transportation (DDOT) Recruiting
Detroit, Michigan, United States, 48226
Detroit Fire Department & Detroit EMS Recruiting
Detroit, Michigan, United States, 48226
Detroit Police Department Recruiting
Detroit, Michigan, United States, 48226
Sponsors and Collaborators
Henry Ford Health System
Investigators
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Principal Investigator: William W O'Neill, MD Henry Ford Health System
Study Director: Dee Dee Wang, MD Henry Ford Health System
  Study Documents (Full-Text)

Documents provided by William W. O'Neill, Henry Ford Health System:
Study Protocol  [PDF] April 19, 2020

Additional Information:
Publications:

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Responsible Party: William W. O'Neill, Director, Center for Structural Heart Disease, Henry Ford Health System
ClinicalTrials.gov Identifier: NCT04341441    
Other Study ID Numbers: 1410401
First Posted: April 10, 2020    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 William W. O'Neill, Henry Ford Health System:
COVID-19
Coronavirus
Healthcare Workers
SARS-CoV 2
First Responders
Emergency Medical Technicians
Paramedics
Firefighters
Police Officers
Detroit
Michigan
Henry Ford Hospital
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents