Will Hydroxychloroquine Impede or Prevent COVID-19

Phase 3

Terminated

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

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

Registration Number: NCT04341441

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 624

Inclusion Criteria

Participant is willing and able to provide informed consent.
Participant is 18-75 years of age.
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.
Participant is willing to provide blood samples for the study.
Subject agrees to all aspects of the study.
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

Does not meet inclusion criteria.
Participant unable or unwilling to provide informed consent.
Participant has any of the symptoms above or screens positive for possible COVID-19 disease.
Participant is currently enrolled in a study to evaluate an investigational drug.
Vulnerable populations deemed inappropriate for study by the site Principal Investigator.
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).
The participant is a woman of childbearing age whose pregnancy status is unknown and is not willing to use 2 methods of contraception.
The participant is pregnant or nursing.
The participant was diagnosed with retinopathy prior to study entry.
The participant has a diagnosis of porphyria prior to study entry.
The participant has renal failure with a creatinine clearance of <10 ml/min, pre-dialysis or requiring dialysis.
The Participant has a family history of Sudden Cardiac Death.
The participant is currently on diuretic therapy.
The participant has a history of known Prolonged QT Syndrome.
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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Drug - Daily Dose	Monitoring Visit - Baseline	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.
Study Drug - Weekly Dose	Monitoring Visit - Week 4	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.
Study Drug - Daily Dose	Monitoring Visit - Week 4	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.
Study Drug - Daily Dose	Monitoring Visit - Week 8	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.
Study Drug - Daily Dose	Weekly Assessment	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.
Study Drug - Weekly Dose	Monitoring Visit - Baseline	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.
Study Drug - Weekly Dose	Monitoring Visit - Week 8	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.
Study Drug - Weekly Dose	Weekly Assessment	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.
Placebo	Placebo oral tablet	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.
Placebo	Monitoring Visit - Baseline	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.
Placebo	Monitoring Visit - Week 4	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.
Placebo	Monitoring Visit - Week 8	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.
Placebo	Weekly Assessment	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.
Non-Randomized Active Comparator	Monitoring Visit - Baseline	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.
Non-Randomized Active Comparator	Monitoring Visit - Week 4	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.
Non-Randomized Active Comparator	Monitoring Visit - Week 8	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.
Non-Randomized Active Comparator	Weekly Assessment	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.
Study Drug - Daily Dose	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.
Study Drug - Weekly Dose	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 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria.

Primary Outcome Measures

Name	Time	Method
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.	8 Weeks	The rate of acquisition of SARS-CoV 2 infections and clinical COVID-19 disease (number of events) in study participants for each randomized hydroxychloroquine treatment arm was compared to the placebo treatment arm. This included both symptomatic and asymptomatic patients.

Secondary Outcome Measures

Name	Time	Method
Examine the Correlation Between HCQ Drug Levels and Development of COVID-19 Symptoms or Positive COVID-19 Test Results.	8 Weeks	Examination of the correlation between HCQ drug levels and development of COVID-19 clinical symptoms and/or positive COVID-19 test results via weekly subject questionnaire and/or blood samples.
Assess the Impact of Chronic Weight-based Dosing of HCQ for COVID-19 Prevention.	8 Weeks	Compare the rates of SARS-CoV 2 infections (number of events of symptomatic patients with a positive COVID-19 test) in the non-randomized comparator arm to the randomized hydroxychloroquine and placebo arms to assess the impact of chronic weight-based dosing of HCQ for COVID-19 prevention via weekly questionnaire and/or blood samples. This analysis includes all randomized and non-randomized groups in the study.
Comparison of the Rate of SARS-CoV 2 Infections as Measured by IgM/IgG Seroconversion in Study Participants Receiving Randomized HCQ Versus Placebo.	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 in the randomized arms of the study (Study Drug - Daily Dose, Study Drug - Weekly Dose, and Placebo).
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.	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.
Determine the Safety and Tolerability of HCQ Dosing for Preventive Strategy Against COVID-19 as Measured by Adverse Events and Serious Adverse Events.	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.
To Examine Other Clinical Factors Contributing to the Risk of SARS-CoV 2 Infection in Healthcare Workers and First Responders.	8 Weeks	Examination of other clinical factors 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.
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.	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.
Determine the Effect of Hydroxychloroquine Dose in the Prevention of COVID-19 Viremia and Disease.	8 Weeks	Compare the rates of SARS-CoV 2 symptomatic infections (number of events with both symptoms and positive test for COVID-19) between the randomized hydroxychloroquine treatment arms and the placebo control arm to determine the effect of HCQ dose in the prevention of COVID-19 viremia and disease. This analysis only includes only the randomized arms in the study (Study Drug - Daily Dose, Study Drug - Weekly Dose, and Placebo).
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.	8 Weeks	Measurement of the seroprevalence of SARS-CoV 2 IgM and/or IgG positive samples in all arms of the study, randomized and non-randomized (Study Drug - Daily Dose, Study Drug - Weekly Dose, Placebo, and Non-Randomized Active Comparator).
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.	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.