PATCH 2&3:Prevention & Treatment of COVID-19 (Severe Acute Respiratory Syndrome Coronavirus 2) With Hydroxychloroquine
NCT ID: NCT04353037
Last Updated: 2021-10-19
Study Results
Results available
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View full resultsBasic Information
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Recruitment Status
TERMINATED
Clinical Phase
PHASE2
Total Enrollment
39 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-04-07
Study Completion Date
2020-07-11
Brief Summary
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The proposed hypothesis is that high doses of hydroxychloroquine (HCQ) for at least 2 weeks can be effective antiviral medication both as a treatment in ambulatory patients and prophylaxis/treatment in health care workers because it impairs lysosomal function and reorganizes lipid raft (cholesterol and sphingolipid rich microdomains in the plasma membrane) content in cells, which are both critical determinants of Emerging Viral Disease (EVD) infection. This hypothesis is based on a growing literature linking chloroquine to antiviral activity. It is estimated that enough information exists to launch a clinical trial of hydroxychloroquine for COVID-19.
Detailed Description
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Sub-Study 1: COVID-19 patients in self-quarantine. Group 1: Hydroxychloroquine 400 mg bid (two 200 mg tablets taken twice a day; totaling 800 mg per day) for two weeks; Group 2: Placebo 2 pills twice a day for two weeks
Sub-Study 2: Asymptomatic health care worker prophylaxis. Group 1: Hydroxychloroquine 600 mg once a day (three 200 mg tablets taken once a day) for up to 2 months; Group 2: Placebo 3 pills once a day for up to 2 months; cross-over from placebo to HCQ 600 mg once a day is allowed upon confirmatory diagnosis for COVID-19.
PRIMARY OBJECTIVES:
Sub-Study 1 (Patients tested for COVID-19 who meet symptomology and age requirements for eligibility): Rate of hospitalization
Sub-Study 2 (Health Care Workers): Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months
SECONDARY OBJECTIVES Sub-Study 1: Rate of secondary infection of co-inhabitants, adverse events, and negative for COVID-19 (confirmed by accepted testing methods) at 14 days
Sub-Study 2: Number of shifts missed; rate of adverse events, and hospitalization at 2 months
Sub-Study 2: Asymptomatic health care worker prophylaxis. Group 1: Hydroxychloroquine 600 mg once a day (three 200 mg tablets taken once a day) for up to 2 months; Group 2: Placebo 3 pills once a day for up to 2 months; cross-over from placebo to HCQ 600 mg once a day is allowed upon confirmatory diagnosis for COVID-19.
PRIMARY OBJECTIVES:
Sub-Study 1 (Patients tested for COVID-19 who meet symptomology and age requirements for eligibility): Rate of hospitalization
Sub-Study 2 (Health Care Workers): Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months
SECONDARY OBJECTIVES Sub-Study 1: Rate of secondary infection of co-inhabitants, adverse events, and negative for COVID-19 (confirmed by accepted testing methods) at 14 days
Sub-Study 2: Number of shifts missed; rate of adverse events, and hospitalization at 2 months
Conditions
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Coronavirus
Corona Virus Infection
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Treatment and prevention study
Primary Study Purpose
TREATMENT
Blinding Strategy
DOUBLE
Participants
Caregivers
For PATCH 2: participant and care provider are blinded. For PATCH 3: Health care worker is blinded.
Study Groups
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Sub Study 1 Patients
Patients tested for COVID-19 who meet symptomology and age requirements for eligibility
Group Type
EXPERIMENTAL
Group 1 HCQ
Intervention Type
DRUG
Enrolled participants randomized in Group 1 receive the HCQ drug
Group 2 Placebo
Intervention Type
DRUG
Enrolled participants randomized in Group 2 will receive a placebo drug
Sub Study 2 Health Care Workers
Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months
Group Type
EXPERIMENTAL
Group 1 HCQ
Intervention Type
DRUG
Enrolled participants randomized in Group 1 receive the HCQ drug
Group 2 Placebo
Intervention Type
DRUG
Enrolled participants randomized in Group 2 will receive a placebo drug
Interventions
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Group 1 HCQ
Enrolled participants randomized in Group 1 receive the HCQ drug
Intervention Type
DRUG
Group 2 Placebo
Enrolled participants randomized in Group 2 will receive a placebo drug
Intervention Type
DRUG
Other Intervention Names
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HCQ Group
Placebo Group
Eligibility Criteria
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Inclusion Criteria
* Able to give informed consent
* Subjects meeting the following criteria by Sub-Study:
Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine.Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment.
Sub-Study 2: Currently employed as a health care worker. Health care workers are defined as :
* Medical Doctor (MD)
* Doctor of Osteopathic Medicine (DO)
* Nurse Practitioner (NP)
* Physician's Assistant (PA)
* Registered Nurse (RN)
* other members of the medical care team with significant COVID-19 exposure;
Health care workers meeting the following criteria:
* asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted);
* scheduled for an average of \>20 hours per week of clinical care over the next 2 months.
Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd.
* Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log).
* Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).
* Participants must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
* Participants must have adequate baseline organ function
* Able to give informed consent
* Subjects meeting the following criteria by Sub-Study:
Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine. Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment.
Sub-Study 2: Currently employed as a health care worker (Medical Doctor, MD; Doctor of Osteopathic Medicine, DO; Nurse Practitioner, NP; Physician's Assistant, PA; and Registered Nurse, RN or other members of the medical care team with significant COVID-19 exposure); asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); scheduled for an average of \>20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd.
* Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log).
* Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2.
* Participant must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
* Participant must have adequate baseline organ function
* Subjects meeting the following criteria by Sub-Study:
Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine.Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment.
Sub-Study 2: Currently employed as a health care worker. Health care workers are defined as :
* Medical Doctor (MD)
* Doctor of Osteopathic Medicine (DO)
* Nurse Practitioner (NP)
* Physician's Assistant (PA)
* Registered Nurse (RN)
* other members of the medical care team with significant COVID-19 exposure;
Health care workers meeting the following criteria:
* asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted);
* scheduled for an average of \>20 hours per week of clinical care over the next 2 months.
Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd.
* Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log).
* Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).
* Participants must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
* Participants must have adequate baseline organ function
* Able to give informed consent
* Subjects meeting the following criteria by Sub-Study:
Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine. Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment.
Sub-Study 2: Currently employed as a health care worker (Medical Doctor, MD; Doctor of Osteopathic Medicine, DO; Nurse Practitioner, NP; Physician's Assistant, PA; and Registered Nurse, RN or other members of the medical care team with significant COVID-19 exposure); asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); scheduled for an average of \>20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd.
* Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log).
* Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2.
* Participant must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
* Participant must have adequate baseline organ function
Exclusion Criteria
* Allergy to hydroxychloroquine
* Pregnant or lactating or positive pregnancy test during pre-medication examination
* Receiving any trial treatment drug for 2019-ncov within 14 days prior to screening evaluation (off label, compassionate use or trial related).
* Known retinal disease including but not limited to macular degeneration, retinal vein occlusion, visual field defect, diabetic retinopathy
* History of interstitial lung disease or chronic pneumonitis unrelated COVID-19.
* Due to risk of disease exacerbation, participants with porphyria or psoriasis are ineligible unless the disease is well-controlled, and they are under the care of a specialist for the disorder who agrees to monitor the Participant for exacerbations.
* Participants with serious intercurrent illness that requires active intravenous therapy, intense monitoring, or frequent dose adjustments for medication including but not limited to infectious disease, cancer, autoimmune disease, cardiovascular disease.
* Participants who have undergone major abdominal, thoracic, spine or central nervous system (CNS) surgery in the last 2 months, or plan to undergo surgery during study participation.
* Participants receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment
* Participants currently taking digoxin
* History or evidence of increased cardiovascular risk including any of the following:
* Left ventricular ejection fraction (LVEF) \< institutional lower limit of normal. Baseline echocardiogram is not required.
* Current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation
* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment
* Current ≥ Class II congestive heart failure as defined by New York Heart Association.
* Deemed unable to participate for medical reasons identified by Co-PI and study staff.
* Pregnant or lactating or positive pregnancy test during pre-medication examination
* Receiving any trial treatment drug for 2019-ncov within 14 days prior to screening evaluation (off label, compassionate use or trial related).
* Known retinal disease including but not limited to macular degeneration, retinal vein occlusion, visual field defect, diabetic retinopathy
* History of interstitial lung disease or chronic pneumonitis unrelated COVID-19.
* Due to risk of disease exacerbation, participants with porphyria or psoriasis are ineligible unless the disease is well-controlled, and they are under the care of a specialist for the disorder who agrees to monitor the Participant for exacerbations.
* Participants with serious intercurrent illness that requires active intravenous therapy, intense monitoring, or frequent dose adjustments for medication including but not limited to infectious disease, cancer, autoimmune disease, cardiovascular disease.
* Participants who have undergone major abdominal, thoracic, spine or central nervous system (CNS) surgery in the last 2 months, or plan to undergo surgery during study participation.
* Participants receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment
* Participants currently taking digoxin
* History or evidence of increased cardiovascular risk including any of the following:
* Left ventricular ejection fraction (LVEF) \< institutional lower limit of normal. Baseline echocardiogram is not required.
* Current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation
* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment
* Current ≥ Class II congestive heart failure as defined by New York Heart Association.
* Deemed unable to participate for medical reasons identified by Co-PI and study staff.
Minimum Eligible Age
18 Years
Maximum Eligible Age
75 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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ProHealth Care Associates
OTHER
Sponsor Role
collaborator
University of Pennsylvania
OTHER
Sponsor Role
collaborator
UnitedHealth Group
INDUSTRY
Sponsor Role
lead
Responsible Party
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Dr. Deneen Vojta
Chief Medical Officer, Research and Development
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Deneen Vojta, MD
Role: PRINCIPAL_INVESTIGATOR
UnitedHealth Group
Locations
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ProHealth New York
New York, New York, United States
Site Status
Countries
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United States
References
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Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
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Rangwala R, Leone R, Chang YC, Fecher LA, Schuchter LM, Kramer A, Tan KS, Heitjan DF, Rodgers G, Gallagher M, Piao S, Troxel AB, Evans TL, DeMichele AM, Nathanson KL, O'Dwyer PJ, Kaiser J, Pontiggia L, Davis LE, Amaravadi RK. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy. 2014 Aug;10(8):1369-79. doi: 10.4161/auto.29118. Epub 2014 May 20.
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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2020-0003
Identifier Type: -
Identifier Source: org_study_id