Will Hydroxychloroquine Impede or Prevent COVID-19
Condition: COVID-19; Coronavirus; Coronavirus Infections; SARS-CoV 2
MeSH terms: COVID-19; Coronavirus Infections
Intervention: Hydroxychloroquine - Daily Dosing; Hydroxychloroquine - Weekly Dosing; Placebo oral tablet; Monitoring Visit - Baseline; Monitoring Visit - Week 4; Monitoring Visit - Week 8; Weekly Assessment
Intervention description: 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.; 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.; 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.; 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.; 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.; 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.; 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.
Intervention MeSH terms: Hydroxychloroquine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
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).
Enrollment: 624.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: COVID-19; Coronavirus; Healthcare Workers; SARS-CoV 2; First Responders; Emergency Medical Technicians; Paramedics; Firefighters; Police Officers; Detroit; Michigan; Henry Ford Hospital

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.
    

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).