Hydroxychloroquine as Chemoprevention for COVID-19 for High Risk Healthcare Workers

• Sponsor: Hackensack Meridian Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT04345653
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arm: 1
• Actual Duration (Months): 12.8
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

The study proposes to conduct an open-label Phase II trial to evaluate the feasibility, safety and early efficacy of hydroxychloroquine (HCQ) administration in reduction of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and development of Corona Virus Disease 2019 (COVID-19) in high-risk, healthy acute care provider participants exposed, directly or indirectly, to COVID-19 patients. There is a more than 50 years track record of safety of HCQ for treatment and prevention of various disease states. Early data on use of HCQ for COVID treatment suggests anti-viral activity and immunomodulatory properties for reducing inflammation associated with COVID-19.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: Hydroxychloroquine Sulfate (HCQ)	Phase 2

Detailed Description

Given the lack of data regarding use of HCQ for COVID-19 prevention in healthy participants in midst of pandemic crisis, this study proposes an expedited feasibility study focusing on safety and early efficacy.

Prior to HCQ administration, baseline SARS-CoV-2 and other baseline biomarker testing will be conducted. During the 4-week study period, participants will be monitored for drug related adverse events and assessed for development of COVID. SARS-CoV-2 assay and biomarker testing will be repeated at the end of four-week study. Safety outcomes will be assessed by the number of adverse events (AEs) and their severity; and early efficacy as the number of participants who tested positive at the end of the 4-week period comparing to data collected by occupational Health regarding the total number of high-risk healthcare workers that were tested positive during the same period and historical controls from known high risk infection rates. An exploratory analysis of inflammatory regulation and immunomodulatory markers by HCQ and its effect on possible disease modification based on previously studied pathophysiological mechanism of COVID-19.

The broader aim of this study is to set a precedent to facilitate a large-scale emergent public health intervention. Purpose would be to mitigate, or abort further transmission of COVID-19. Given that COVID-19 transmission has occurred prior to initiation of this study, the rationale for this intervention is based on prior epidemiological evidence. Post-infectious or vaccination-induced immunity in at least 30% of population at-risk has been shown to mitigate or abort propagation of a local epidemics and global pandemic. This would help flatten the curve of the disease progression, until such time that a vaccine may become available. Data from this study will be used to design and implement a population-based phase IIb/III randomized clinical trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Feasibility, Safety and Early Efficacy Trial of Hydroxychloroquine as Primary Prevention of Corona Virus Disease 2019 in High Risk Health Care Providers
• Actual Study Start Date: Apr 14, 2020
• Actual Primary Completion Date: Jun 5, 2020
• Actual Study Completion Date: May 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study arm - Hydroxychloroquine Sulfate (HCQ) HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth	Drug: Hydroxychloroquine Sulfate (HCQ); Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.

Outcome Measures

Primary Outcome Measures

1. Recruitment Feasibility [Study period, up to two months from the day the first participant was screened]

   To evaluate the feasibility of this protocol including participants' recruitment within the estimated time frame, i.e. understand the ability of the team to identify eligible participants, enroll them, retain them and follow them up until study completion.

2. Resource Utilization [Study period, up to two months from the day the first participant was screened]

   To evaluate the utilization of tests and drug for this study in consideration with the limited availability of both for research purposes as reflected on the number of participants that got tested and received at least one dose of the drug.

3. Safety as Reflected on the Number and Severity of Adverse Events and Serious Adverse Events [28 day post enrollment]

   To Determine the Safety profile for a previously well studied drug in this select group of HCP. Incidence of well described side effects would be studied over the course of the study and will be compared with the side effects and their prevalence as described in the Pharmacy manual for HCQ.

4. Early Feasibility as Reflected on the Number of Participants Contracting COVID-19 (10% or Less) in Comparison to the Expected 30% as Per CDC. [28 day post enrollment]

   To evaluate the early efficacy of HCQ in high-risk, healthy volunteers in the prevention of acquiring COVID-19 while continuing to follow standard precautions that meet or exceed Centers of Disease Control (CDC) guidelines.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Volunteers ages 18 to 99 years,

• Able to sign own informed consent form,

• Considered high-risk healthcare care providers in a hospital setting with active exposure to COVID-19 infection.

High-risk healthcare providers are defined as those actively working during the study duration in the Emergency Department and in the Intensive Care Setting, for the purpose of this study.

Exclusion Criteria:

• Inability to tolerate an oral medication or known allergy to chloroquine or hydroxychloroquine

• Pregnancy or breast-feeding

• Immunocompromised status, hepatic failure, electrolytic imbalance

• Creatinine clearance (CCL) <30 mL/min

• Prolonged QT interval (QTc > 450ms for males and QTc > 470 for females)

• Confirmed COVID-19 infection on baseline testing

• Has another known contraindication to treatment with the study drug, including retinopathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hackensack Meridian Health - JFK Medical Center	Edison	New Jersey	United States	08820

Sponsors and Collaborators

• Hackensack Meridian Health

Investigators

• Principal Investigator: Jawad Kirmani, MD, Hackensack Meridian Health Corporation

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 30, 2020

More Information

Publications

None provided.

• Responsible Party: Hackensack Meridian Health
• ClinicalTrials.gov Identifier: NCT04345653
• Other Study ID Numbers: Pro2020-0356
• First Posted: Apr 14, 2020
• Last Update Posted: May 12, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Hackensack Meridian Health: covid19; workers; prevention
• Additional relevant MeSH terms: COVID-19; Hydroxychloroquine

Study Results

Participant Flow

Arm/Group Title	Study Arm - Hydroxychloroquine Sulfate (HCQ)
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Period Title: Overall Study
STARTED	48
COMPLETED	46
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Study Arm - Hydroxychloroquine Sulfate (HCQ)
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Overall Participants	46
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	46 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	39.5
Sex: Female, Male (Count of Participants)
Female	29 63%
Male	17 37%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 8.7%
Not Hispanic or Latino	42 91.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	23 50%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 6.5%
White	16 34.8%
More than one race	0 0%
Unknown or Not Reported	4 8.7%
Region of Enrollment (participants) [Number]
United States	46 100%

Outcome Measures

1. Primary Outcome

Title	Recruitment Feasibility
Description	To evaluate the feasibility of this protocol including participants' recruitment within the estimated time frame, i.e. understand the ability of the team to identify eligible participants, enroll them, retain them and follow them up until study completion.
Time Frame	Study period, up to two months from the day the first participant was screened

Outcome Measure Data

Analysis Population Description

High risk healthcare providers

Arm/Group Title	Study Arm
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Measure Participants	46
Count of Participants [Participants]	46 100%

2. Primary Outcome

Title	Resource Utilization
Description	To evaluate the utilization of tests and drug for this study in consideration with the limited availability of both for research purposes as reflected on the number of participants that got tested and received at least one dose of the drug.
Time Frame	Study period, up to two months from the day the first participant was screened

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Arm - Hydroxychloroquine Sulfate (HCQ)
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Measure Participants	46
Count of Participants [Participants]	46 100%

3. Primary Outcome

Title	Safety as Reflected on the Number and Severity of Adverse Events and Serious Adverse Events
Description	To Determine the Safety profile for a previously well studied drug in this select group of HCP. Incidence of well described side effects would be studied over the course of the study and will be compared with the side effects and their prevalence as described in the Pharmacy manual for HCQ.
Time Frame	28 day post enrollment

Outcome Measure Data

Analysis Population Description

High risk healthcare providers

Arm/Group Title	Study Arm - Hydroxychloroquine Sulfate (HCQ)
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Measure Participants	46
Serious Adverse events	0
Adverse events	24

4. Primary Outcome

Title	Early Feasibility as Reflected on the Number of Participants Contracting COVID-19 (10% or Less) in Comparison to the Expected 30% as Per CDC.
Description	To evaluate the early efficacy of HCQ in high-risk, healthy volunteers in the prevention of acquiring COVID-19 while continuing to follow standard precautions that meet or exceed Centers of Disease Control (CDC) guidelines.
Time Frame	28 day post enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Arm - Hydroxychloroquine Sulfate (HCQ)
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Measure Participants	46
Number [participants]	0 0%

Adverse Events

Time Frame	Overall follow up period: 6 month
Arm/Group Title	Study Arm - Hydroxychloroquine Sulfate (HCQ)
Arm/Group Description	HCQ sulfate HCQ 400mg (2x 200mg tablets) by mouth 6-12 hours apart on day 1, followed by 3 weeks of weekly 400mg (2x 200mg tablets) by mouth Hydroxychloroquine Sulfate (HCQ): Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
All Cause Mortality
	Study Arm - Hydroxychloroquine Sulfate (HCQ)
	Affected / at Risk (%)	# Events
Total	0/46 (0%)
Serious Adverse Events
	Study Arm - Hydroxychloroquine Sulfate (HCQ)
	Affected / at Risk (%)	# Events
Total	0/46 (0%)
Other (Not Including Serious) Adverse Events
	Study Arm - Hydroxychloroquine Sulfate (HCQ)
	Affected / at Risk (%)	# Events
Total	24/46 (52.2%)
Cardiac disorders
Shortness of breath and chest pain	4/46 (8.7%)	4
Gastrointestinal disorders
Abdominal pain	2/46 (4.3%)	2
Diarrhea	5/46 (10.9%)	5
Nausea	3/46 (6.5%)	3
General disorders
Fatigue	4/46 (8.7%)	4
Nervous system disorders
Headaches	3/46 (6.5%)	3
Psychiatric disorders
Mood Disorder	2/46 (4.3%)	2
Skin and subcutaneous tissue disorders
Rash	2/46 (4.3%)	2
Alopecia	1/46 (2.2%)	1

Limitations/Caveats

[Not Specified]

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.