PATCH 2&3:Prevention & Treatment of COVID-19 (Severe Acute Respiratory Syndrome Coronavirus 2) With Hydroxychloroquine

Study Overview
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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

Official Title
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PATCH 2 & 3: (Prevention and Treatment of COVID-19 With Hydroxychloroquine) A Double-blind Placebo Controlled Randomized Trial of Hydroxychloroquine in the Prevention and Treatment of COVID-19

Conditions
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Coronavirus, Corona Virus Infection

Intervention / Treatment
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* Drug: Group 1 HCQ
* Drug: Group 2 Placebo


Participation Criteria
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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 Exclusion Criteria: 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 (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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment and prevention study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sub Study 1 Patients<br>Patients tested for COVID-19 who meet symptomology and age requirements for eligibility | Drug: Group 1 HCQ<br>* Enrolled participants randomized in Group 1 receive the HCQ drug<br>* Other names: HCQ Group;Drug: Group 2 Placebo<br>* Enrolled participants randomized in Group 2 will receive a placebo drug<br>* Other names: Placebo Group;|
| Experimental: Sub Study 2 Health Care Workers<br>Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months | Drug: Group 1 HCQ<br>* Enrolled participants randomized in Group 1 receive the HCQ drug<br>* Other names: HCQ Group;Drug: Group 2 Placebo<br>* Enrolled participants randomized in Group 2 will receive a placebo drug<br>* Other names: Placebo Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized | Number of COVID-19+ PCR patients in self-quarantine who are hospitalized up to 31 days after beginning HCQ or Placebo | Until completion of study, 29 to 31 days after beginning treatment. | 
| Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months | Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months | Until completion of study, 2 months after start of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine | Co-inhabitants of COVID-19 positive PCR patients in self-quarantine that test positive up to 31 days after patient begins treatment with HCQ or Placebo | Until completion of study, 29 to 31 days after beginning treatment. | 
| Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine | 15-17 days after completion of 14 day treatment | 
| Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine | Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine | 1-3 days after completion of 14 day treatment | 
| Sub Study 2:Health Care Workers:Number of Shifts Missed | Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period | up to  60 days after enrollment | 
| Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the  60 Day Active Period | Assessment of any medical events that occur during the  60 day active period that is felt to be related to receipt of HCQ | Until completion of study, 2 months ( 60 days) after start of treatment. | 
| Sub Study 2:Health Care Workers:Rate of Hospitalization | if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period | Until completion of study, 2 months after start of treatment. |