Clinical trial NCT04352946: HEalth Care Worker pROphylaxis Against COVID-19: The HERO Trial
Official title: Protecting Health Care Workers From COVID-19 With Hydroxychloroquine Pre-exposure Prophylaxis: A Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Prophylaxis
COVID-19
Health Care Worker
Hydroxychloroquine
Lead sponsor: GeoSentinel Foundation
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 374
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: HCW are randomized to either the study drug (HCQ) or placebo.
Primary purpose: PREVENTION

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative Incidence of COVID-19 Infection
timeFrame: 90 days
Secondary outcomes:
measure: Adverse events incidence
timeFrame: 90 days
measure: Duration of symptomatic COVID-19 disease
timeFrame: 90 days
measure: Days hospitalized attributed to COVID-19
timeFrame: 90 days
measure: Number or respiratory failure attributable to COVID-19 disease
timeFrame: 90 days
measure: Mortality Incidence
timeFrame: 90 days
measure: Days of work lost
timeFrame: 90 days
Other outcomes:
measure: Proportion of HCW with plasma able to neutralize SARS-CoV-2 virus
timeFrame: 90 days
measure: Number of participants with severity markers of host immune and endothelial activation
timeFrame: 90 days
Locations:
city: New York
country: United States
facility: The New York Center for Travel and Tropical Medicine
state: New York
Study officials:
affiliation: Dr. Bradley A. Connor
name: Bradley A Connor, MD
role: PRINCIPAL_INVESTIGATOR
References: