HEalth Care Worker pROphylaxis Against COVID-19: The HERO Trial (HERO)

Protecting Health Care Workers From COVID-19 With Hydroxychloroquine Pre-exposure Prophylaxis: A Randomized, Placebo-controlled Trial

This is a double-blinded, randomized placebo-controlled trial to determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily, for health care workers in the hospital reduces symptomatic and asymptomatic COVID-19 disease during the pandemic. 374 health care workers will be randomized at a 1:1 allocation between the intervention and placebo arms and followed for 90 days. The cumulative incidence of COVID-19 infection in the intervention group will be compared to the cumulative incidence of COVID-19 in the placebo group with relative (risk ratio and 95% CI) and absolute measures (risk difference and 95% CI).

Study Overview

• Status: Unknown
• Conditions: COVID-19; Prophylaxis; Hydroxychloroquine; Health Care Worker
• Intervention / Treatment: Drug: Hydroxychloroquine Pre-Exposure Prophylaxis; Drug: Placebo oral tablet

Detailed Description

This is a double-blinded, randomized placebo-controlled trial to determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily, for health care workers in the hospital reduces symptomatic and asymptomatic COVID-19 disease during the pandemic.

Secondary outcomes include 1) Adverse events; 2) Duration of symptomatic COVID-19 disease; 3) Days hospitalized attributed to COVID-19; 4) Respiratory failure attributable to COVID-19 disease requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; 5) Mortality attributed to COVID-19 disease, and; 6) Number of days unable to work attributed to COVID-19. Laboratory markers within participants with confirmed COVID-19 will also be explored.

A total of 374 HCW will be randomized using a fixed 1:1 allocation ratio with randomization in permuted block of varying sizes from four to eight will be used to ensure equal allocation to each group. The study population will be health care workers at the New York Presbyterian Hospital - Cornell Campus and they will participate in the study for 90 days.

To determine if the intervention has been successful, the cumulative incidence of COVID-19 infection in the intervention group will be compared to the cumulative incidence of COVID-19 in the placebo group with relative (risk ratio and 95% CI) and absolute measures (risk difference and 95% CI). Investigators will also calculate adjusted risk ratios and risk differences including job class as a covariate and any other baseline clinical and demographic characteristics that are not balanced between the treatment and placebo arms using a log-binomial regression model.

• Study Type: Interventional
• Enrollment (Anticipated): 374
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10022
      • The New York Center for Travel and Tropical Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Health care worker (HCW) at the hospital who work on a "full time" basis during the study period. For the purposes of the study, "health care workers" are physicians, nurses, nurse practitioners, physician assistants, respiratory therapists, X-ray technicians, social workers and support staff (including but not limited to house-keeping, and porters).
2. Age ≥18 years.
3. Ability to communicate with study staff in English

Exclusion Criteria:

1. Known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds.
2. Current use of hydroxychloroquine for the treatment of a medical condition.
3. Known prolonged QT syndrome, or concomitant medications which simultaneously may prolong the QTC that cannot be temporarily suspended/replaced. These are including but not limited to Class IA, IC and III antiarrhythmics; certain antidepressants, antipsychotics, and anti-infectives; domperidone; 5-hydroxytryptamine (5-HT)3 receptor antagonists; kinase inhibitors; histone deacetylase inhibitors beta-2 adrenoceptor agonists.
4. Known pre-existing retinopathy of the eye.
5. Disclosure of self-administered use of hydroxychloroquine or chloroquine currently under investigation <4 weeks prior to study. This window is intended to account for the drug half-life of HCQ (21 days).
6. Baseline symptom of COVID-19 disease at enrollment and baseline viral detection specimen positive for SARS-COV-2. All participants with COVID-19 symptoms at enrollment will be directed to have confirmatory testing (within the department or occupational health as per the site guidelines). Participants who are negative for SARS-COV-2 will be redirected to enrollment procedures, those testing positive will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrocholoroquine Pre-exposure prophylaxis; HCQ will be administered as 400mg orally once for 60 days.	Drug: Hydroxychloroquine Pre-Exposure Prophylaxis; HCQ PreP 400mg daily; Other Names: HCQ PreP; Hydroxychloroquine PreP
Placebo Comparator: Placebo; Placebo will be administered as 400mg orally once for 60 days.	Drug: Placebo oral tablet; Placebo tablets 400mg daily; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of COVID-19 Infection	Incidence of symptomatic and asymptomatic COVID-19 infection in health care workers	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events incidence	Incidence of reported and grade of adverse events	90 days
Duration of symptomatic COVID-19 disease	Duration in days of symptomatic COVID-19 disease in HCW who had disease	90 days
Days hospitalized attributed to COVID-19	Duration in days of hospitalization attributed to COVID-19 disease in HCW who had disease	90 days
Number or respiratory failure attributable to COVID-19 disease	Number of HCW with respiratory failure attributable to COVID-19 disease requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation in HCW who developed disease	90 days
Mortality Incidence	Cumulative Incidence of Mortality attributed to COVID-19 disease in HCW who developed disease	90 days
Days of work lost	Number of days unable to work attributed to COVID-19 in HCW who developed disease	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of HCW with plasma able to neutralize SARS-CoV-2 virus	Proportion of participants with plasma able to neutralize SARS-CoV-2 virus (plaque reduction neutralization test) in vitro.	90 days
Number of participants with severity markers of host immune and endothelial activation	Number of participants with severity markers of host immune and endothelial activation measured at clinical presentation and their ability to predict severity and outcome.	90 days

Collaborators and Investigators

• Sponsor: GeoSentinel Foundation
• Investigators: Principal Investigator: Bradley A Connor, MD, Dr. Bradley A. Connor

Publications and helpful links

Helpful Links

• coronavirus references

Study record dates

Study Major Dates

• Study Start (Anticipated): April 24, 2020
• Primary Completion (Anticipated): June 24, 2020
• Study Completion (Anticipated): August 24, 2020

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: April 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: GFICOVID-19-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: supporting made available to other researchers
• IPD Sharing Time Frame: From July 1, 2020 until December 31, 2020
• IPD Sharing Access Criteria: from our web site
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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