Hydroxychloroquine in the Prevention of COVID-19 Infection in Healthcare Workers

• Sponsor: Baylor Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT04333225
• Collaborator: (none)
• Enrollment: 221
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.9
• Patients Per Site Per Month: 76.4

Study Details

Study Description

Brief Summary

In order to assess the efficacy of hydroxychloroquine treatment weekly for a total of 7 weeks in the prevention of COVID-19 infection, three hundred sixty (360) Healthcare workers with high risk exposure to patients infected with COVID-19 will be tested for COVID-19 infection via nasopharyngeal (NP) swab once weekly for 7 weeks. Of those, one hundred eighty (180) will receive weekly doses of hydroxychloroquine for the duration of the study. Subjects who opt not to receive the study drug will form the control group.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Hydroxychloroquine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Prospective Clinical Study of Hydroxychloroquine in the Prevention of SARS- CoV-2 (COVID-19) Infection in Healthcare Workers After High-risk Exposures
• Actual Study Start Date: Apr 3, 2020
• Actual Primary Completion Date: Jun 30, 2020
• Actual Study Completion Date: Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydroxychloroquine Subjects who chose to enter the HCQ arm received a loading dose of 800 mg HCQ on day 1 followed by two 200 mg tablets once a week for a total of 7 weeks	Drug: Hydroxychloroquine; Weekly treatment in individuals at high risk; Other Names: Plaquenil HCQ
No Intervention: Control Subjects who declined taking HCQ were considered as controls

Outcome Measures

Primary Outcome Measures

1. Number of Participants Infected With COVID-19 or COVID-19 Like Illness During the Trial [Up to 7 weeks after study initiation]

   Number of participants infected with COVID-19 or identified as having COVID-19 like illness during the trial

Secondary Outcome Measures

1. Time From Study Initiation Until the Occurrence of COVID-19 or COVID-19 Like Illness or Being Censored [Up to 7 weeks after study initiation]

   Time-to-first clinical event consisting of a persistent change for any of the following: diagnosis of COVID-19 clinical characteristics of COVID-19 like illness being censored

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Adult male and female healthcare workers ≥ 18 to ≤ 75 years of age upon study consent

2. Healthcare workers with

• One day or more of exposure to suspect and/or positive COVID-19 patients, including but not limited to those working in the Emergency Department or Intensive Care Unit.

OR

• Unprotected exposure to a known positive COVID-19 patient within 72 hours of screening.

1. Afebrile with no constitutional symptoms

2. Willing and able to comply with scheduled visits, treatment plan, and other study procedures

3. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any subject-mandated procedures

Exclusion Criteria:

1. Participation in other investigational clinical trials for the treatment or prevention of SARS-COV-2 infection within 30days

2. Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during Screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested Note: the following criteria follow standard clinical practice for FDA approved indications of this medication

3. Having a prior history of blood disorders such as aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia

4. Having a prior history of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency

5. Having dermatitis, psoriasis or porphyria

6. Taking Digoxin, Mefloquine, methotrexate, cyclosporine, praziquantel, antacids and kaolin, cimetidine, ampicillin, Insulin or antidiabetic drugs, arrhythmogenic drugs, antiepileptic drugs, loop, thiazide, and related diuretics, laxatives and enemas, amphotericin B, high dose corticosteroids, and proton pump inhibitors, neostigmine, praziquantel, Pyridostigmine, tamoxifen citrate

7. Allergies: 4-Aminoquinolines

8. Pre-existing retinopathy of the eye

9. Has a chronic liver disease or cirrhosis, including hepatitis B and/or untreated hepatitis

10. Untreated or uncontrolled active bacterial, fungal infection

11. Known or suspected active drug or alcohol abuse, per investigator judgment

12. Women who are pregnant or breastfeeding

13. Known hypersensitivity to any component of the study drug

14. A known history of prolonged QT syndrome or history of additional risk factors for torsades de pointe (e.g., heart failure, requires a lab test , family history of Long QT Syndrome), or the use of concomitant medications that prolong the QT/QTc interval

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor University Medical Center	Dallas	Texas	United States	75226

Sponsors and Collaborators

• Baylor Research Institute

Investigators

• Principal Investigator: Peter A McCullough, MD, MPH, Baylor Health Care System

Study Documents (Full-Text)

• Study Protocol - May 28, 2020
• Statistical Analysis Plan - May 28, 2020

More Information

Publications

None provided.

• Responsible Party: Baylor Research Institute
• ClinicalTrials.gov Identifier: NCT04333225
• Other Study ID Numbers: 020-132
• First Posted: Apr 3, 2020
• Last Update Posted: Aug 20, 2021
• Last Verified: May 1, 2020

• 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 Baylor Research Institute: hydroxychloroquine
• Additional relevant MeSH terms: COVID-19; Hydroxychloroquine

Study Results

Participant Flow

Recruitment Details	All study subjects were employed by and worked at the Baylor University Medical Center in Dallas, Texas.

Arm/Group Title	Hydroxychloroquine	Control
Arm/Group Description	Subjects who chose to enter the HCQ arm received a loading dose of 800 mg HCQ on day 1 followed by two 200 mg tablets once a week for a total of 7 weeks	Subjects who declined taking HCQ were considered as controls
Period Title: Overall Study
STARTED	101	120
COMPLETED	98	115
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Hydroxychloroquine	Control	Total
Arm/Group Description	Subjects who chose to enter the HCQ arm received a loading dose of 800 mg HCQ on day 1 followed by two 200 mg tablets once a week for a total of 7 weeks	Subjects who declined taking HCQ were considered as controls	Total of all reporting groups
Overall Participants	101	120	221
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.90 (12.42)	34.53 (800)	35.36 (11.05)
Sex: Female, Male (Count of Participants)
Female	66 65.3%	101 84.2%	167 75.6%
Male	35 34.7%	19 15.8%	54 24.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 15.8%	26 21.7%	42 19%
Not Hispanic or Latino	85 84.2%	94 78.3%	179 81%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	4 4%	4 3.3%	8 3.6%
White	78 77.2%	104 86.7%	182 82.4%
Others	19 18.8%	12 10%	31 14%
Region of Enrollment (participants) [Number]
United States	101 100%	120 100%	221 100%
Cough score (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	2.74 (7.66)	3.26 (7.46)	3.02 (7.54)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Infected With COVID-19 or COVID-19 Like Illness During the Trial
Description	Number of participants infected with COVID-19 or identified as having COVID-19 like illness during the trial
Time Frame	Up to 7 weeks after study initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Control
Arm/Group Description	Subjects who chose to enter the HCQ arm received a loading dose of 800 mg HCQ on day 1 followed by two 200 mg tablets once a week for a total of 7 weeks	Subjects who declined taking HCQ were considered as controls
Measure Participants	101	120
Count of Participants [Participants]	13 12.9%	32 26.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Control
	Comments
	Type of Statistical Test	Other
	Comments	Other: estimating risk reduction
Statistical Test of Hypothesis	p-Value	0.0112
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.0718
	Confidence Interval	(2-Sided) 95%; 1.15 to 3.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time From Study Initiation Until the Occurrence of COVID-19 or COVID-19 Like Illness or Being Censored
Description	Time-to-first clinical event consisting of a persistent change for any of the following: diagnosis of COVID-19 clinical characteristics of COVID-19 like illness being censored
Time Frame	Up to 7 weeks after study initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Control
Arm/Group Description	Subjects who chose to enter the HCQ arm received a loading dose of 800 mg HCQ on day 1 followed by two 200 mg tablets once a week for a total of 7 weeks	Subjects who declined taking HCQ were considered as controls
Measure Participants	101	120
Mean (Standard Deviation) [Days]	43.17 (11.15)	39.25 (15.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Control
	Comments
	Type of Statistical Test	Other
	Comments	Other: Estimating hazard ratio
Statistical Test of Hypothesis	p-Value	0.0105
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.17 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	7 weeks
Arm/Group Title	Hydroxychloroquine		Control
Arm/Group Description	Subjects who chose to enter the HCQ arm received a loading dose of 800 mg HCQ on day 1 followed by two 200 mg tablets once a week for a total of 7 weeks		Subjects who declined taking HCQ were considered as controls
All Cause Mortality
	Hydroxychloroquine		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		0/120 (0%)
Serious Adverse Events
	Hydroxychloroquine		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/101 (1%)		0/120 (0%)
Infections and infestations
COVID-19 like illness	1/101 (1%)	1	0/120 (0%)	0
Other (Not Including Serious) Adverse Events
	Hydroxychloroquine		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/101 (20.8%)		0/120 (0%)
Gastrointestinal disorders
Nausea	13/101 (12.9%)	21	0/120 (0%)	0
Diarrhea	8/101 (7.9%)	21	0/120 (0%)	0

Limitations/Caveats

Due to the off-label use of HCQ, we were not able to incorporate randomization in our design. The outcome of CLI was based on self-reported symptoms, which is prone to bias. The trial may be under-powered as recruitment was forced to stop early at 221 instead of 360 because of the demand for and subsequent shortage of HCQ in March 2020. Our study participants were young and healthy compared to other prophylaxis trials, which may partially explain the low rates of COVID-19.

More Information

Certain Agreements

Principal Investigators are NOT 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.