The PATCH Trial (Prevention And Treatment of COVID-19 With Hydroxychloroquine) (PATCH)

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Hydroxychloroquine Sulfate 400 mg twice a day; Drug: Hydroxychloroquine Sulfate 600 mg twice a day; Drug: Hydroxychloroquine Sulfate 600 mg once a day

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: Hydroxychloroquine Sulfate 400 mg twice a day; Antimalarial compound; Other Names: Plaquenil
Placebo Comparator: 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.	Drug: Placebo oral tablet; Placebo; Other Names: Placebo
Experimental: 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	Drug: Hydroxychloroquine Sulfate 600 mg twice a day; Antimalarial compound; Other Names: Plaquenil
Active Comparator: 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	Drug: Hydroxychloroquine Sulfate 600 mg once a day; Antimalarial compound; Other Names: Plaquenil
Experimental: 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	Drug: Hydroxychloroquine Sulfate 600 mg once a day; Antimalarial compound; Other Names: Plaquenil
Placebo Comparator: 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.	Drug: Placebo oral tablet; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	until quarantine release or hospitalization
Time to Hospital Discharge	Cohort 2 (hospitalized COVID-19 patients): median number of days until hospital discharge	until hospital discharge
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	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Housemate Infection	Cohort 1 rate of participant-reported secondary infection of housemates	until quarantine release, or approximately <20 days
Rate of Hospitalization	Cohort 1 rate of hospitalization	until quarantine release

Collaborators and Investigators

• Sponsor: Ravi Amaravadi, MD
• Investigators: Principal Investigator: Ravi Amaravadi, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Abella BS, Jolkovsky EL, Biney BT, Uspal JE, Hyman MC, Frank I, Hensley SE, Gill S, Vogl DT, Maillard I, Babushok DV, Huang AC, Nasta SD, Walsh JC, Wiletyo EP, Gimotty PA, Milone MC, Amaravadi RK; Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Investigators. Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial. JAMA Intern Med. 2021 Feb 1;181(2):195-202. doi: 10.1001/jamainternmed.2020.6319.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2020
• Primary Completion (Actual): November 11, 2020
• Study Completion (Actual): November 13, 2020

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 842838

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We will publish our results in a peer-reviewed journal and make available de-identified data for additional analysis
• IPD Sharing Time Frame: One year after study completion
• IPD Sharing Access Criteria: Open access
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• 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