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

• ClinicalTrials.gov Identifier: NCT04329923
• Recruitment Status: Recruiting
• First Posted: April 1, 2020
• Last Update Posted: April 28, 2020
• Sponsor: Ravi Amaravadi, MD
• Information provided by (Responsible Party): Ravi Amaravadi, MD, University of Pennsylvania

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Hydroxychloroquine Sulfate 400 mg twice a day; Drug: Hydroxychloroquine Sulfate 600 mg twice a day; Drug: Hydroxychloroquine Sulfate 600 mg once a day; Drug: Placebo oral tablet	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: There are 3 cohorts. All partcipants in of each the cohorts are randomized to one of two arms
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Cohorts 1 and 3 are double-blind placebo control cohorts. Cohort 2 is an open label randomized study
• Primary Purpose: Treatment
• Official Title: The PATCH Trial (Prevention And Treatment of COVID-19 With Hydroxychloroquine)
• Actual Study Start Date: April 9, 2020
• Estimated Primary Completion Date: April 1, 2021
• Estimated Study Completion Date: December 1, 2021

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Median release from quarantine time [ Time Frame: 14 days or less ]
   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 days have elapsed since the beginning of symptom onset.
2. Rate of hospital discharge [ Time Frame: 14 days ]
   Cohort 2 (hospitalized COVID-19 patients): Rate of participants discharged at or before 14 days
3. Rate of infection [ Time Frame: 2 months ]
   Cohort 3 Physicians and nurse prophylaxis: Rate of COVID-19 infection at 2 months

Secondary Outcome Measures :

1. Rate of housemate infection [ Time Frame: 14 days ]
   Cohort 1 rate of participant-reported secondary infection of housemates
2. Rate of hospitalization [ Time Frame: 14 days ]
   Cohort 1 rate of hospitalization
3. Cohort 1 adverse event rate [ Time Frame: 14 days ]
   Cohort 1 rate of treatment related adverse events
4. Time to condition appropriate for discharge [ Time Frame: 14 days ]
   Cohort 2 Time to condition appropriate for discharge. The primary care team indicates the patients has improved to the point of being discharged.
5. Rate of ICU admission [ Time Frame: 14 days ]
   Cohort 2 rate of ICU admission from a floor bed in the hospital
6. Time to PCR negativity [ Time Frame: 14 days ]
   Cohort 2 the number of days between hospital admission and a negative PCR test for SARS-CoV-2.
7. Cohort 2 adverse events [ Time Frame: 14 days ]
   Cohort 2 rate of treatment related adverse events
8. Scheduled shifts missed [ Time Frame: 2 months ]
   Cohort 3 number of scheduled shifts at the hospital that are missed.
9. Cohort 3 adverse events [ Time Frame: 2 months ]
   Cohort 3 rate of treatment related adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Amelia Anderson; 215-509-5690; amelia.anderson@pennmedicine.upenn.edu

Locations

United States, Pennsylvania

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Amelia Anderson 215-509-5690 amelia.anderson@pennmedicine.upenn.edu

Principal Investigator: Ravi Amaravadi, MD

Sponsors and Collaborators

Ravi Amaravadi, MD

Investigators

• Principal Investigator: Ravi Amaravadi, MD; University of Pennsylvania

More Information

• Responsible Party: Ravi Amaravadi, MD, Associate Professor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04329923
• Other Study ID Numbers: 842838
• First Posted: April 1, 2020
• Last Update Posted: April 28, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

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

• 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

Additional relevant MeSH terms:

Hydroxychloroquine; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents