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.
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
Drug: Group 1 HCQ
Enrolled participants randomized in Group 1 receive the HCQ drug
Other Name: HCQ Group
Drug: Group 2 Placebo
Enrolled participants randomized in Group 2 will receive a placebo drug
Other Name: Placebo Group
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.
ProHealth New York
New York, New York, United States
Deneen Vojta, MD, Principal Investigator
UnitedHealth Group