Does Hydroxychloroquine Before & During Patient Exposure Protect Healthcare Workers From Coronavirus?

NCT04374942 | Terminated Phase 3 DMC

• 2 other identifiers: HEROs Protocol 1.5ISRCTN14326006
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

On 11 March 2020, the World Health Organization declared SARS-CoV-2 (commonly called COVID-19) a global pandemic. As in any pandemic, maintaining the health and safety of the healthcare workforce is of great importance as health care workers (HCW) remain a critical line of defence against the spread of COVID-19 and play a vital role in the recovery of those already infected. Frontline HCW, such as those in the emergency department (ED), are at high risk of contracting COVID-19 due to their close proximity to patients who may have the virus. The impact of frontline HCW becoming ill and thus unable to go to work is equally high, and of grave risk to the function of the healthcare system and the ability to minimize the impact of the current pandemic. This study aims to evaluate whether hydroxychloroquine (HCQ), a well-tolerated drug typically used in the prevention of malaria transmission and rheumatic disease, taken before and during exposure to patients with COVID-19, is effective at reducing COVID-19 infections among ED health care workers.

Conditions

Pre-Exposure Prophylaxis; Coronavirus; SARS-CoV 2

Keywords

Hydroxychloroquine; PrEP; Pre-exposure Prophylaxis; COVID-19; Coronavirus; SARS-CoV 2

Outcome Measures

Primary Outcomes (1)

• Microbiologically confirmed COVID-19 (SARS-CoV-2 infection)

  This is a composite endpoint which includes any positive result from a validated SARS-CoV-2 diagnostic assay including detection of viral RNA, or seroconversion by day 104 (14 days after end of the randomization period).

  Samples collected at day 0, 30, 60, 90 and 120

Secondary Outcomes (8)

• Adverse events

  Assessed at day 30, 60, 90, and day 120

• Symptom duration of COVID-19

  Collected every 7 days from day 7 to day 120

• Days of hospitalization attributable to COVID-19

  Collected every 7 days from day 7 to day 120

• Respiratory failure requiring ventilatory support attributable to COVID-19

  Collected every 7 days from day 7 to day 120

• Mortality

  Collected every 7 days from day 7 to day 120

Study Arms (2)

Study drug arm

EXPERIMENTAL

50% of participants will be randomized to the study drug arm, and will take 400mg hydroxychloroquine orally once a day for three months (Day 1-90).

Drug: Hydroxychloroquine

Placebo arm

PLACEBO COMPARATOR

50% of participants will be randomized to the placebo arm, and will take placebo orally once a day for three months (Day 1-90).

Drug: Placebo oral tablet

Interventions

Hydroxychloroquine DRUG

Oral Hydroxychloroquine, 400 mg taken once daily, for three months as pre-exposure prophylaxis to prevent COVID-19 in health care workers in the emergency department.

Study drug arm

Placebo oral tablet DRUG

Placebo pill (same formula as Hydroxychloroquine without active ingredient) taken once daily, for three months.

Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Health care worker (HCW) in the emergency department who is anticipated to work at least 10 shifts over the duration of the study period (minimum 6 hours per shift) and anticipated to remain in the emergency department for the duration of the study (i.e., not transferring to another unit). For the purposes of the study, "health care workers" are physicians (including residents), nurses, nurse practitioners, physician assistants, respiratory therapists, X-ray technicians, social workers and support staff (including but not limited to house-keeping, and porters).
• Age ≥18 years.
• Ability to communicate with study staff in English

You may not qualify if:

• Currently pregnant, planning to become pregnant during the study period, and/or breast feeding
• Known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds.
• Current use of hydroxychloroquine for the treatment of a medical condition.
• 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.
• Known pre-existing retinopathy.
• Disclosure of self-administered use of hydroxychloroquine or chloroquine within 12 weeks prior to study. This window allows five half-lives of HCQ (i.e. 21 days) to pass before being reintroduced to the drug.
• Confirmed symptomatic COVID-19 at time of enrollment, i.e. symptom of COVID-19 at enrollment with confirmation of SARS-CoV-2 infection by viral detection as performed according to local guidelines for symptomatic HCWs. 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.

Sponsors & Collaborators

• Megan Landes: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G2C4, Canada

Location

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Megan Landes, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Kevin Kain, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This trial is fully-blinded, at the level of the participant, study coordinator, and investigator. Study drug and placebo will be identical in appearance and will be provided by the manufacturer. They will be packaged in identical bottles and dispensed by the Research Clinical Trials Pharmacy at UHN.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Physician, Emergency Department

Model Details: The HEROS study is a double-blind, randomized placebo controlled trial of oral HCQ 400 mg taken once daily for three months as PrEP to prevent COVID-19 in health care workers in the emergency department.

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 5, 2020
• Study Start: April 30, 2020
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: April 29, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)