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

Henry Ford Health

Status and phase: Terminated; Phase 3

Conditions: COVID-19; SARS-CoV 2; Coronavirus Infections; Coronavirus

Treatments: Diagnostic Test: Monitoring Visit - Week 8; Drug: Hydroxychloroquine - Weekly Dosing; Other: Weekly Assessment; Diagnostic Test: Monitoring Visit - Baseline; Other: Placebo oral tablet; Diagnostic Test: Monitoring Visit - Week 4; Drug: Hydroxychloroquine - Daily Dosing

Study type: Interventional

Funder types: Other

Identifiers

NCT04341441

1410401

Details and patient eligibility

About

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.

Full 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.

Enrollment: 624 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

624 participants in 4 patient groups

Study Drug - Daily Dose

Active Comparator group

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.

Treatment:

Drug: Hydroxychloroquine - Daily Dosing

Other: Weekly Assessment

Diagnostic Test: Monitoring Visit - Week 4

Diagnostic Test: Monitoring Visit - Baseline

Diagnostic Test: Monitoring Visit - Week 8

Study Drug - Weekly Dose

Active Comparator group

Description:

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.

Treatment:

Other: Weekly Assessment

Diagnostic Test: Monitoring Visit - Week 4

Diagnostic Test: Monitoring Visit - Baseline

Drug: Hydroxychloroquine - Weekly Dosing

Diagnostic Test: Monitoring Visit - Week 8

Placebo

Active Comparator group

Description:

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.

Treatment:

Other: Weekly Assessment

Diagnostic Test: Monitoring Visit - Week 4

Diagnostic Test: Monitoring Visit - Baseline

Other: Placebo oral tablet

Diagnostic Test: Monitoring Visit - Week 8

Non-Randomized Active Comparator

Active Comparator group

Description:

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.

Treatment:

Other: Weekly Assessment

Diagnostic Test: Monitoring Visit - Week 4

Diagnostic Test: Monitoring Visit - Baseline

Diagnostic Test: Monitoring Visit - Week 8