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

• Sponsor: Ravi Amaravadi, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04329923
• Collaborator: (none)
• Enrollment: 173
• Location: 1
• Arms: 6
• Actual Duration (Months): 7.2
• Patients Per Site Per Month: 24.2

Study Details

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
• Actual Enrollment: 173 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 armsThere 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: Apr 9, 2020
• Actual Primary Completion Date: Nov 11, 2020
• Actual Study Completion Date: Nov 13, 2020

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 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

Outcome Measures

Primary Outcome Measures

1. 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.

2. Time to Hospital Discharge [until hospital discharge]

   Cohort 2 (hospitalized COVID-19 patients): median number of days until hospital discharge

3. 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 Outcome Measures

1. Rate of Housemate Infection [until quarantine release, or approximately <20 days]

   Cohort 1 rate of participant-reported secondary infection of housemates

2. Rate of Hospitalization [until quarantine release]

   Cohort 1 rate of hospitalization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Ravi Amaravadi, MD

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jun 23, 2020
• Statistical Analysis Plan - Jun 23, 2020

More Information

Publications

None provided.

• Responsible Party: Ravi Amaravadi, MD, Associate Professor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04329923
• Other Study ID Numbers: 842838
• First Posted: Apr 1, 2020
• Last Update Posted: Dec 10, 2020
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: COVID-19; Hydroxychloroquine

Study Results

Participant Flow

Arm/Group Title	Cohort 1 HCQ	Cohort 1 Placebo	Cohort 2 HCQ High Dose	Cohort 2 HCQ Low Dose	Cohort 3 HCQ	Cohort 3 Placebo
Arm/Group Description	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	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	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	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	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	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
Period Title: Overall Study
STARTED	17	17	4	3	66	66
COMPLETED	16	13	3	2	64	61
NOT COMPLETED	1	4	1	1	2	5

Baseline Characteristics

Arm/Group Title	Cohort 1 HCQ	Cohort 1 Placebo	Cohort 2 HCQ High Dose	Cohort 2 HCQ Low Dose	Cohort 3 HCQ	Cohort 3 Placebo	Total
Arm/Group Description	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	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	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	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	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	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	Total of all reporting groups
Overall Participants	17	17	4	3	66	66	173
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	49	65	48	31	34	40
Sex: Female, Male (Count of Participants)
Female	12 70.6%	9 52.9%	2 50%	3 100%	54 81.8%	33 50%	113 65.3%
Male	5 29.4%	8 47.1%	2 50%	0 0%	12 18.2%	33 50%	60 34.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	7 10.6%	7 10.6%	14 8.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	8 47.1%	11 64.7%	3 75%	3 100%	3 4.5%	1 1.5%	29 16.8%
White	6 35.3%	3 17.6%	1 25%	0 0%	55 83.3%	56 84.8%	121 69.9%
More than one race	0 0%	0 0%	0 0%	0 0%	1 1.5%	2 3%	3 1.7%
Unknown or Not Reported	3 17.6%	3 17.6%	0 0%	0 0%	0 0%	0 0%	6 3.5%

Outcome Measures

1. Primary Outcome

Title	Time to Release From Quarantine Time
Description	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

Outcome Measure Data

Analysis Population Description

randomized patients that were released from quarantine on study

Arm/Group Title	Cohort 1 HCQ	Cohort 1 Placebo
Arm/Group Description	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	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
Measure Participants	15	13
Median (Full Range) [days]	8	11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1 HCQ, Cohort 1 Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.58
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time to Hospital Discharge
Description	Cohort 2 (hospitalized COVID-19 patients): median number of days until hospital discharge
Time Frame	until hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 2 HCQ High Dose	Cohort 2 HCQ Low Dose
Arm/Group Description	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	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
Measure Participants	4	3
Median (Full Range) [days]	5.5	4

3. Primary Outcome

Title	Number of Health Care Workers Who Developed SARS-COV-2 Infection
Description	Cohort 3 Physicians and nurse prophylaxis: Rate of COVID-19 infection at 2 months
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 3 HCQ	Cohort 3 Placebo
Arm/Group Description	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	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
Measure Participants	64	61
Count of Participants [Participants]	4 23.5%	4 23.5%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 HCQ	Cohort 1 Placebo
Arm/Group Description	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	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
Measure Participants	17	17
Count of Participants [Participants]	2 11.8%	2 11.8%

5. Secondary Outcome

Title	Rate of Hospitalization
Description	Cohort 1 rate of hospitalization
Time Frame	until quarantine release

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 HCQ	Cohort 1 Placebo
Arm/Group Description	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	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
Measure Participants	17	17
Count of Participants [Participants]	1 5.9%	0 0%

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	All adverse events were grade 1-2 by CTCAE v5.0
Arm/Group Title	Cohort 1 HCQ		Cohort 1 Placebo		Cohort 2 HCQ High Dose		Cohort 2 HCQ Low Dose		Cohort 3 HCQ		Cohort 3 Placebo
Arm/Group Description	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		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		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		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		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		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
All Cause Mortality
	Cohort 1 HCQ		Cohort 1 Placebo		Cohort 2 HCQ High Dose		Cohort 2 HCQ Low Dose		Cohort 3 HCQ		Cohort 3 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)		0/4 (0%)		0/3 (0%)		0/66 (0%)		0/66 (0%)
Serious Adverse Events
	Cohort 1 HCQ		Cohort 1 Placebo		Cohort 2 HCQ High Dose		Cohort 2 HCQ Low Dose		Cohort 3 HCQ		Cohort 3 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		0/17 (0%)		0/4 (0%)		0/3 (0%)		0/66 (0%)		0/66 (0%)
Infections and infestations
hospitalization	1/17 (5.9%)	1	0/17 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/66 (0%)	0	0/66 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort 1 HCQ		Cohort 1 Placebo		Cohort 2 HCQ High Dose		Cohort 2 HCQ Low Dose		Cohort 3 HCQ		Cohort 3 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/17 (35.3%)		3/17 (17.6%)		0/4 (0%)		1/3 (33.3%)		29/66 (43.9%)		15/66 (22.7%)
Gastrointestinal disorders
Abdominal pain	0/17 (0%)	0	2/17 (11.8%)	2	0/4 (0%)	0	0/3 (0%)	0	4/66 (6.1%)	4	0/66 (0%)	0
Anorexia	2/17 (11.8%)	2	1/17 (5.9%)	1	0/4 (0%)	0	0/3 (0%)	0	7/66 (10.6%)	7	2/66 (3%)	2
Diarrhea	3/17 (17.6%)	3	1/17 (5.9%)	1	0/4 (0%)	0	1/3 (33.3%)	1	21/66 (31.8%)	21	8/66 (12.1%)	8
Nausea	6/17 (35.3%)	6	2/17 (11.8%)	2	0/4 (0%)	0	1/3 (33.3%)	1	6/66 (9.1%)	6	5/66 (7.6%)	5

Limitations/Caveats

Sub-study 1 was terminated early after the first interim analysis due to slow accrual Sub-study 2 was terminated early after the first 7 patients based on the recommendation of UPenn research oversight committees Sub-study 3 was terminated early due to meeting futility criteria on a pre-specified second interim analysis

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.