COVID-19
Conditions
Brief summary
The PATCH trial (Prevention And Treatment of COVID-19 with Hydroxychloroquine) is funded investigator-initiated trial that includes 3 cohorts. Cohort 1: a double-blind placebo controlled trial of high dose HCQ as a treatment for home bound COVID-19 positive patients; Cohort 2: a randomized study testing different doses of HCQ in hospitalized patients; Cohort 3: a double blind placebo controlled trial of low dose HCQ as a preventative medicine in health care workers.
Interventions
DRUGHydroxychloroquine Sulfate 400 mg twice a day
Antimalarial compound
DRUGHydroxychloroquine Sulfate 600 mg twice a day
Antimalarial compound
DRUGHydroxychloroquine Sulfate 600 mg once a day
Antimalarial compound
DRUGPlacebo oral tablet
Placebo
Sponsors
Ravi Amaravadi, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Cohorts 1 and 3 are double-blind placebo control cohorts. Cohort 2 is an open label randomized study
Intervention model description
There are 3 cohorts. All partcipants in of each the cohorts are randomized to one of two arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥ 18 years old (Sub-studies 2 and 3) * Competent and capable to provide informed consent * Have access to a smart device such as a cell phone, tablet, laptop computer with necessary data/internet accessibility * Subjects meeting the following criteria by Sub-Study Sub-Study 1: * Age ≥40 years since the risk of prolonged disease that progresses to severe COVID-19 disease increases with age. * PCR-positive for the SARS-CoV2 virus * (Fever, and cough, or Fever and shortness of breath, * ≤4 days since the first symptoms of COVID-19 and date of testing * Not taking azithromycin * Not requiring hospitalization and is sent home for quarantine. * Must live within 30 miles of HUP or Penn Presbytarian Medical Center to facilitate drop-off of medication * Must own a working computer, or smartphone and have internet access * Must be willing to fill out a daily symptom diary * Must be available for a daily phone call, * Must take their own temperature twice a day * Must be willing to report the observed symptoms and development of COVID-19 in the co-inhabitants of the residence at which the quarantine will be served. Sub-Study 2 Hospitalized non-ICU service patients. * PCR-positive for SARS-CoV-2 * Patients admitted to a floor bed at Hospital of the University of Pennsylvania or Penn Presbyterian. * One or more of the following risk factors for progression to severe disease including: immunocompromising conditions, structural lung disease, hypertension, coronary artery disease, diabetes, age \> 60, ferritin \> 850, CRP \> 6, D-dimer \> 1000 Sub-Study 3 Health Care Worker Prevention * Emergency Medicine or Infectious Disease Team physician or nurse at HUP or PPMC * ≥20 hours per week of clinical work scheduled in the coming 2 months during the COVID-19 pandemic * No fever, cough, or shortness of breath in the past 2 weeks * Willing to report compliance with HCQ in the form of a diary * Patients 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.
Exclusion criteria
\<18 years of age * Prisoners or other detained persons * Allergy to hydroxychloroquine Pregnant or lactating or positive pregnancy test * Receiving any treatment drug for 2019-ncov within 14 days prior to screening evaluation (off label, compassionate use or trial related). * Co-enrollment onto another COVID-19 study is not allowed unless there is approval by the Medical Monitor in consultation with the PI and EM and ID sub-I leaders. * Known history of retinal disease including but not limited to age related macular degeneration. * Taking any of the following medications that prolong Qtc: Chlorpromazine.Haloperidol, Droperidol, Quetiapine, Olanzapine. Amisulpride. Thioridazine * History of interstitial lung disease or chronic pneumonitis unrelated COVID-19. * Due to risk of disease exacerbation patients 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 patient for exacerbations. * Patients with serious intercurrent illness that requires active infusional therapy, intense monitoring, or frequent dose adjustments for medication including but not limited to infectious disease, cancer, autoimmune disease, cardiovascular disease. * Patients who have undergone major abdominal, thoracic, spine or CNS surgery in the last 2 months, or plan to undergo surgery during study participation. * Patients 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 * 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. * A QT interval corrected for heart rate using the Frederica formula \> 500 msec (Sub-study 2) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Release From Quarantine Time | until quarantine release or hospitalization | Cohort 1 (home quarantined COVID-19 patients): Median time to release from quarantine by meeting the following criteria: 1) No fever for 72 hours 2) improvement in other symptoms and 3) 7 or 10 days (depending on CDC guidance at the time) have elapsed since the beginning of symptom onset. |
| Time to Hospital Discharge | until hospital discharge | Cohort 2 (hospitalized COVID-19 patients): median number of days until hospital discharge |
| Number of Health Care Workers Who Developed SARS-COV-2 Infection | 2 months | Cohort 3 Physicians and nurse prophylaxis: Rate of COVID-19 infection at 2 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Housemate Infection | until quarantine release, or approximately <20 days | Cohort 1 rate of participant-reported secondary infection of housemates |
| Rate of Hospitalization | until quarantine release | Cohort 1 rate of hospitalization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 HCQ COVID-19 PCR+ patients quarantined at home randomized to this arm will be treated with hydroxychloroquine 400 mg twice a day for up to 14 days
Hydroxychloroquine Sulfate 400 mg twice a day: Antimalarial compound | 17 |
| Cohort 1 Placebo COVID-19 PCR+ patients quarantined at home randomized to this arm will be treated with placebo twice a day for up to 14 days. Crossover is allowed if symptoms worsen after 7 days of treatment.
Placebo oral tablet: Placebo | 17 |
| Cohort 2 HCQ High Dose Hospitalized COVID-19 PCR+ patients randomized to this arm will be treated with hydroxychloroquine 600 mg twice a day for up to 14 days
Hydroxychloroquine Sulfate 600 mg twice a day: Antimalarial compound | 4 |
| Cohort 2 HCQ Low Dose Hospitalized COVID-19 PCR+ patients randomized to this arm will be treated with hydroxychloroquine 600 mg once a day for up to 7 days
Hydroxychloroquine Sulfate 600 mg once a day: Antimalarial compound | 3 |
| Cohort 3 HCQ Health care workers at high risk of contracting COVID-19 randomized to this arm will be treated with hydroxychloroquine 600 mg once a day for 2 months
Hydroxychloroquine Sulfate 600 mg once a day: Antimalarial compound | 66 |
| Cohort 3 Placebo Health care workers at high risk of contracting COVID-19 randomized to this arm will be treated with placebo for 2 month. Crossover is allowed if subject becomes SARS-CoV2 positive.
Placebo oral tablet: Placebo | 66 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | early termination of study | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | positive SARS-COV2 PCR at baseline | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 4 | 1 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 HCQ | Total | Cohort 3 Placebo | Cohort 3 HCQ | Cohort 2 HCQ Low Dose | Cohort 2 HCQ High Dose | Cohort 1 Placebo |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56 years | 40 years | 34 years | 31 years | 48 years | 65 years | 49 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 14 Participants | 7 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 29 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 6 Participants | 121 Participants | 56 Participants | 55 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 12 Participants | 113 Participants | 33 Participants | 54 Participants | 3 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 60 Participants | 33 Participants | 12 Participants | 0 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 4 | 0 / 3 | 0 / 66 | 0 / 66 |
| other Total, other adverse events | 6 / 17 | 3 / 17 | 0 / 4 | 1 / 3 | 29 / 66 | 15 / 66 |
| serious Total, serious adverse events | 1 / 17 | 0 / 17 | 0 / 4 | 0 / 3 | 0 / 66 | 0 / 66 |
Outcome results
Primary
Number of Health Care Workers Who Developed SARS-COV-2 Infection
Cohort 3 Physicians and nurse prophylaxis: Rate of COVID-19 infection at 2 months
Time frame: 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 HCQ | Number of Health Care Workers Who Developed SARS-COV-2 Infection | 4 Participants |
| Cohort 1 Placebo | Number of Health Care Workers Who Developed SARS-COV-2 Infection | 4 Participants |
Primary
Time to Hospital Discharge
Cohort 2 (hospitalized COVID-19 patients): median number of days until hospital discharge
Time frame: until hospital discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 HCQ | Time to Hospital Discharge | 5.5 days |
| Cohort 1 Placebo | Time to Hospital Discharge | 4 days |
Primary
Time to Release From Quarantine Time
Cohort 1 (home quarantined COVID-19 patients): Median time to release from quarantine by meeting the following criteria: 1) No fever for 72 hours 2) improvement in other symptoms and 3) 7 or 10 days (depending on CDC guidance at the time) have elapsed since the beginning of symptom onset.
Time frame: until quarantine release or hospitalization
Population: randomized patients that were released from quarantine on study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 HCQ | Time to Release From Quarantine Time | 8 days |
| Cohort 1 Placebo | Time to Release From Quarantine Time | 11 days |
p-value: 0.28Regression, Cox
Secondary
Rate of Hospitalization
Cohort 1 rate of hospitalization
Time frame: until quarantine release
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 HCQ | Rate of Hospitalization | 1 Participants |
| Cohort 1 Placebo | Rate of Hospitalization | 0 Participants |
Secondary
Rate of Housemate Infection
Cohort 1 rate of participant-reported secondary infection of housemates
Time frame: until quarantine release, or approximately <20 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 HCQ | Rate of Housemate Infection | 2 Participants |
| Cohort 1 Placebo | Rate of Housemate Infection | 2 Participants |