WHIP COVID-19: Will Hydroxychloroquine Impede or Prevent COVID-19
Sponsor
Henry Ford Health System (Other)
Overall Status
Terminated
CT.gov ID
NCT04341441
Collaborator
(none)
624
1
4
8.3
75.4
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
624 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.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
:
Apr 7, 2020
Actual Primary Completion Date
:
Dec 15, 2020
Actual Study Completion Date
:
Dec 15, 2020
Arms and Interventions
| 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:
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 Names:
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 Names:
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 Names:
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 Names:
|
| 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 Names:
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 Names:
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 Names:
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 Names:
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 Names:
|
| 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 Names:
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 Names:
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 Names:
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 Names:
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 Names:
|
| 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 Names:
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 Names:
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 Names:
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 Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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).
- 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).
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
Sponsors and Collaborators
- Henry Ford Health System
Investigators
- 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)
More Information
Publications
- Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, Wang M. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. 2020 Apr 14;323(14):1406-1407. doi: 10.1001/jama.2020.2565.
- Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol. 2012 Apr;42(2):145-53. doi: 10.1007/s12016-010-8243-x. Review.
- Chang, Xu H, Rebaza A, Sharma L, Dela Cruz CS. Protecting health-care workers from subclinical coronavirus infection. Lancet Respir Med. 2020 Mar;8(3):e13. doi: 10.1016/S2213-2600(20)30066-7. Epub 2020 Feb 13.
- Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.
- Howard DR, Brown JM, Todd S, Gregory WM. Recommendations on multiple testing adjustment in multi-arm trials with a shared control group. Stat Methods Med Res. 2018 May;27(5):1513-1530. doi: 10.1177/0962280216664759. Epub 2016 Sep 19.
- Lim HS, Im JS, Cho JY, Bae KS, Klein TA, Yeom JS, Kim TS, Choi JS, Jang IJ, Park JW. Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrob Agents Chemother. 2009 Apr;53(4):1468-75. doi: 10.1128/AAC.00339-08. Epub 2009 Feb 2.
- Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020.
- Mohammad S, Clowse MEB, Eudy AM, Criscione-Schreiber LG. Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients. Arthritis Care Res (Hoboken). 2018 Mar;70(3):481-485. doi: 10.1002/acr.23296. Epub 2018 Feb 9.
- Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005 Aug 22;2:69.
- Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.
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:
Apr 10, 2020
Last Update Posted:
Jun 21, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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,
Director, Center for Structural Heart Disease,
Henry Ford Health System
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator (HCQ Cohort) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | This non-randomized comparator group is comprised of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of standard of care for autoimmune disease(s). |
| Period Title: Overall Study | ||||
| STARTED | 197 | 201 | 200 | 26 |
| COMPLETED | 188 | 199 | 191 | 26 |
| NOT COMPLETED | 9 | 2 | 9 | 0 |
Baseline Characteristics
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). | Total of all reporting groups |
| Overall Participants | 197 | 201 | 200 | 26 | 624 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
45.1
(11.5)
|
45.7
(11.7)
|
43.7
(12.7)
|
45.8
(11.7)
|
44.9
(12.0)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
117
59.4%
|
110
54.7%
|
120
60%
|
23
88.5%
|
370
59.3%
|
| Male |
80
40.6%
|
91
45.3%
|
80
40%
|
3
11.5%
|
254
40.7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Black |
11
5.6%
|
5
2.5%
|
10
5%
|
6
23.1%
|
32
5.1%
|
| White |
163
82.7%
|
179
89.1%
|
169
84.5%
|
18
69.2%
|
529
84.8%
|
| AS/IN/PI |
15
7.6%
|
10
5%
|
15
7.5%
|
2
7.7%
|
42
6.7%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
197
100%
|
201
100%
|
200
100%
|
26
100%
|
624
100%
|
Outcome Measures
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Count of Participants [Participants] |
1
0.5%
|
1
0.5%
|
1
0.5%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Study Drug - Daily Dose, Study Drug - Weekly Dose, Placebo, Non-Randomized Active Comparator |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Sample size was determined with one planned interim analysis when 50% of participants had completed their 8 weeks of treatment using an O'Brien-Fleming alpha spending method to ensure an overall type 1 error of 0.05. With a sample size of 900 per group and alpha = 0.0492, the power to detect a 32% reduction in COVID-19 disease rate (10% vs 6.8%) between the placebo and HCQ treated groups, determined at 87%. Study required 1000 per group with a total of 3000 patients to complete the trial. | |
| Statistical Test of Hypothesis | p-Value | 0.75 |
| Comments | P-value for the comparison between groups, including the non-randomized active comparator, was 0.75. | |
| Method | Mantel Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.32 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Low number of primary events precluded estimated value of risk ratio. | |
| Title | Determine the Effect of Hydroxychloroquine Dose in the Prevention of COVID-19 Viremia and Disease. |
|---|---|
| Description | 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). |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. |
| Measure Participants | 188 | 199 | 191 |
| Count of Participants [Participants] |
1
0.5%
|
1
0.5%
|
1
0.5%
|
| Title | Assess the Impact of Chronic Weight-based Dosing of HCQ for COVID-19 Prevention. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis outcome measure reports the number of occurrences of symptomatic patients with a positive COVID-19 test in all randomized and non-randomized groups in the study. |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Count of Participants [Participants] |
1
0.5%
|
1
0.5%
|
1
0.5%
|
0
0%
|
| Title | Comparison of the Rate of SARS-CoV 2 Infections as Measured by IgM/IgG Seroconversion in Study Participants Receiving Randomized HCQ Versus Placebo. |
|---|---|
| Description | 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). |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis is only for the randomized arms of the study (Study Drug - Daily Dose, Study Drug - Weekly Dose, and Placebo). |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. |
| Measure Participants | 188 | 199 | 191 |
| Count of Participants [Participants] |
1
0.5%
|
1
0.5%
|
2
1%
|
| Title | 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. |
|---|---|
| Description | 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). |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis reports the number of patient samples that seroconverted to positive serology for IgM and/or IgG by the subject end of study time point in all arms of the study, randomized and non-randomized (Study Drug - Daily Dose, Study Drug - Weekly Dose, Placebo, and Non-Randomized Active Comparator). |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Count of Participants [Participants] |
1
0.5%
|
1
0.5%
|
2
1%
|
0
0%
|
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients were asymptomatic at study entry by observed lack of symptoms and consistent with study eligibility criteria. This analysis planned to evaluate patients who tested positive for COVID-19 at study entry time point, but had yet to develop symptoms when entering the study to assess efficacy of hydroxychloroquine in preventing symptom emergence. Only one participant met the criteria for outcome measure analysis. |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Count of Participants [Participants] |
1
0.5%
|
0
0%
|
0
0%
|
0
0%
|
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Determine the Safety and Tolerability of HCQ Dosing for Preventive Strategy Against COVID-19 as Measured by Adverse Events and Serious Adverse Events. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 26 |
| Adverse events (only Level 1 and 2) observed in the study. |
206
|
193
|
188
|
2
|
| Serious adverse events (Level 3 or 4). |
0
|
0
|
0
|
0
|
| Title | To Examine Other Clinical Factors Contributing to the Risk of SARS-CoV 2 Infection in Healthcare Workers and First Responders. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to low number of events, this analysis was not performed. No factors were identified. |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Number [Clinical factors] |
NA
|
NA
|
NA
|
NA
|
| Title | Examine the Correlation Between HCQ Drug Levels and Development of COVID-19 Symptoms or Positive COVID-19 Test Results. |
|---|---|
| Description | 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. |
| Time Frame | 8 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis was not performed due to low number of events and early termination of the study. Therefore, no data or measures to report. |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Number [Correlation coefficient] |
NA
|
NA
|
NA
|
NA
|
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis was not performed due to low number of events and early termination of the study. Therefore, no data or markers to report. |
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | 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. This 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). |
| Measure Participants | 188 | 199 | 191 | 25 |
| Number [Inflammatory markers] |
NA
|
NA
|
NA
|
NA
|
Adverse Events
| Time Frame | 8 weeks. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator (HCQ Cohort) | ||||
| Arm/Group Description | 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. | 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. All treatment groups will receive placebo pills to have the patients take 2 pills a day. | 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. 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. | This non-randomized comparator group is comprised of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for autoimmune disease(s). | ||||
All Cause Mortality |
||||||||
| Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator (HCQ Cohort) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/188 (0%) | 0/199 (0%) | 0/191 (0%) | 0/26 (0%) | ||||
Serious Adverse Events |
||||||||
| Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator (HCQ Cohort) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/188 (0%) | 0/199 (0%) | 0/191 (0%) | 0/26 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Study Drug - Daily Dose | Study Drug - Weekly Dose | Placebo | Non-Randomized Active Comparator (HCQ Cohort) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 97/188 (51.6%) | 95/199 (47.7%) | 85/191 (44.5%) | 2/26 (7.7%) | ||||
| Cardiac disorders | ||||||||
| All cardiac symptoms reported | 16/188 (8.5%) | 17 | 15/199 (7.5%) | 16 | 10/191 (5.2%) | 10 | 0/26 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| All ear and labyrinth symptoms reported | 9/188 (4.8%) | 10 | 6/199 (3%) | 9 | 8/191 (4.2%) | 8 | 0/26 (0%) | 0 |
| Eye disorders | ||||||||
| All eye symptoms reported | 6/188 (3.2%) | 9 | 1/199 (0.5%) | 1 | 6/191 (3.1%) | 6 | 0/26 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| All gastrointestinal symptoms reported | 36/188 (19.1%) | 54 | 34/199 (17.1%) | 43 | 42/191 (22%) | 52 | 0/26 (0%) | 0 |
| General disorders | ||||||||
| All general symptoms and administration site symptoms reported | 8/188 (4.3%) | 9 | 13/199 (6.5%) | 15 | 15/191 (7.9%) | 17 | 0/26 (0%) | 0 |
| Immune system disorders | ||||||||
| All immune system symptoms reported | 4/188 (2.1%) | 4 | 5/199 (2.5%) | 6 | 0/191 (0%) | 0 | 0/26 (0%) | 0 |
| Infections and infestations | ||||||||
| All infection and infestation symptoms reported | 8/188 (4.3%) | 8 | 1/199 (0.5%) | 1 | 3/191 (1.6%) | 3 | 0/26 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Injury, poisoning and procedural complication symptoms reported | 3/188 (1.6%) | 3 | 1/199 (0.5%) | 2 | 1/191 (0.5%) | 1 | 1/26 (3.8%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Metabolism and nutrition symptoms reported | 1/188 (0.5%) | 1 | 0/199 (0%) | 0 | 0/191 (0%) | 0 | 0/26 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| All Musculoskeletal and connective tissue symptoms reported | 11/188 (5.9%) | 13 | 16/199 (8%) | 17 | 14/191 (7.3%) | 16 | 1/26 (3.8%) | 1 |
| Nervous system disorders | ||||||||
| All nervous system symptoms reported | 41/188 (21.8%) | 43 | 30/199 (15.1%) | 33 | 34/191 (17.8%) | 42 | 0/26 (0%) | 0 |
| Psychiatric disorders | ||||||||
| All psychiatric symptoms reported | 5/188 (2.7%) | 6 | 10/199 (5%) | 13 | 7/191 (3.7%) | 7 | 0/26 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| All reproductive system and breast symptoms reported | 0/188 (0%) | 0 | 0/199 (0%) | 0 | 2/191 (1%) | 2 | 0/26 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| All respiratory, thoracic and mediastinal symptoms reported | 13/188 (6.9%) | 17 | 22/199 (11.1%) | 27 | 15/191 (7.9%) | 21 | 0/26 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| All skin and subcutaneous tissue symptoms reported | 11/188 (5.9%) | 12 | 7/199 (3.5%) | 10 | 3/191 (1.6%) | 3 | 0/26 (0%) | 0 |
Limitations/Caveats
Study has been terminated. Interim analysis did not reveal any safety concerns by the DSMB with hydroxychloroquine treatment, but unblinded data did not provide support to continue due to low numbers of events. Event rate did not meet projected magnitude; given low recruitment potential, it is unlikely that a positive result will occur.
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | John McKinnon, MD, MSc |
|---|---|
| Organization | Henry Ford Health System |
| Phone | 313-916-8828 |
| jmckinn3@hfhs.org |
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:
Apr 10, 2020
Last Update Posted:
Jun 21, 2022
Last Verified:
Jun 1, 2022