Clinical trial NCT04341441: Will Hydroxychloroquine Impede or Prevent COVID-19
Official title: Will Hydroxychloroquine Impede or Prevent COVID-19: WHIP COVID-19 Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Coronavirus
Coronavirus Infections
SARS-CoV 2
Keywords: COVID-19
Coronavirus
Healthcare Workers
SARS-CoV 2
First Responders
Emergency Medical Technicians
Paramedics
Firefighters
Police Officers
Detroit
Michigan
Henry Ford Hospital
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 624
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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.

Eligibility 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).

Primary outcomes:
measure: To Determine if the Use of Hydroxychloroquine as Preventive Therapy Decreases the Rate of Acquisition of SARS-CoV 2 Infections With Clinical COVID-19 Disease in Study Participants for Each Randomized Treatment Arm as Compared to Placebo.
timeFrame: 8 Weeks
Secondary outcomes:
measure: Determine the Effect of Hydroxychloroquine Dose in the Prevention of COVID-19 Viremia and Disease.
timeFrame: 8 Weeks
measure: Assess the Impact of Chronic Weight-based Dosing of HCQ for COVID-19 Prevention.
timeFrame: 8 Weeks
measure: Comparison of the Rate of SARS-CoV 2 Infections as Measured by IgM/IgG Seroconversion in Study Participants Receiving Randomized HCQ Versus Placebo.
timeFrame: 8 Weeks
measure: Compare the Seroprevalence of SARS-CoV 2 IgM and/or IgG Positive Samples at Study Entry and Study Conclusion in All Participants Receiving HCQ Compared to Those Receiving Placebo.
timeFrame: 8 Weeks
measure: 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.
timeFrame: 8 Weeks
measure: 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.
timeFrame: 8 Weeks
measure: Determine the Safety and Tolerability of HCQ Dosing for Preventive Strategy Against COVID-19 as Measured by Adverse Events and Serious Adverse Events.
timeFrame: 8 Weeks
measure: To Examine Other Clinical Factors Contributing to the Risk of SARS-CoV 2 Infection in Healthcare Workers and First Responders.
timeFrame: 8 Weeks
measure: Examine the Correlation Between HCQ Drug Levels and Development of COVID-19 Symptoms or Positive COVID-19 Test Results.
timeFrame: 8 Weeks
measure: 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.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
Study officials:
affiliation: Henry Ford Health System
name: William W O'Neill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Health System
name: Dee Dee Wang, MD
role: STUDY_DIRECTOR
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