Does Hydroxychloroquine Before & During Patient Exposure Protect Healthcare Workers From Coronavirus? (HEROs)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04374942|
Recruitment Status : Enrolling by invitation
First Posted : May 5, 2020
Last Update Posted : May 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pre-Exposure Prophylaxis Coronavirus SARS-CoV 2||Drug: Hydroxychloroquine Drug: Placebo oral tablet||Phase 3|
On March 11th, 2020, the World Health Organization (WHO) declared coronavirus disease (COVID-19) caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) a pandemic. As of March 22, 2020 there have been over 267,013 confirmed cases and 11,201 deaths in 185 different countries or regions; it is quickly overwhelming health care systems worldwide to detrimental effect. Even with current moderate interventions imposed, estimates predict that 10-18% of the Canadian population will be infected with the virus by its peak in July. Health care workers (HCWs) remain a critical line of defence in the fight against this pandemic and maintaining their health is not only an important social responsibility of the government, but it is also of vital national interest to treat and control others infected with this virus or sick with other disease.
Estimates from China indicate that HCWs make up 3.8% of cases, while in Italy it is reported to be much higher - 8.3%. Early numbers from front-line workers in Italy suggested up to 20% of HCWs become infected with COVID-19, and these rates are approximately 3 times higher than the general population. When HCWs become sick, not only do they risk dying, but they also must take weeks away from work limiting the ability of the health care system to function. The fear associated with becoming ill also causes higher rates of missed work and higher rates of burnout, as seen with previous outbreaks. It is also now clear that asymptomatic transmission of COVID-19 not only occurs, but may even be the most important factor in spread of the virus. HCWs may therefore become vectors of viral spread to those who are the most vulnerable in other areas of the hospital. Preventing HCWs from acquiring SARS-CoV-2 should therefore be of the utmost importance to national interests.
Repurposing drugs already known to be safe and tolerable in humans provides a major advantage in a pandemic where time is critical. Of candidate drugs, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), have shown some promise. Originally an anti-malarial medication, CQ exerts direct antiviral effects by inhibiting pH-dependent steps of the replication of several viruses, including coronaviruses. It also has immunomodulatory effects, suppressing the release of TNFα and IL-6, which are involved in the inflammatory complications of several viral diseases. In vitro data has shown that CQ potently blocks virus infection at low micromolar concentrations with a high selectivity index. CQ is also widely distributed throughout the body, including the lungs, after oral administration. An early clinical trial of more than 100 COVID-19 patients in China reported that CQ was superior to placebo in inhibiting pneumonia, improving lung imaging, promoting viral seroconversion, and shortening the disease course, although data was not released. Based on those results experts in China recommended CQ 500mg twice daily for ten days in all patients with COVID-19. HCQ has also been shown to also have anti-SARS-CoV-2 activity in vitro and may actually be more potent. It has a better safety profile than CQ (during long term use), and allows a higher daily dose, with fewer concerns of drug-drug interactions. Preliminary clinical data also suggests that HCQ may lead to significantly faster viral clearance in COVID-19 patients as assessed by nasopharyngeal swab (70% vs. 12.5%, p=0.001).
Pre-exposure prophylaxis (PrEP) offers the ability to protect front-line HCWs from illness, decrease nosocomial spread of SARS-CoV-2, and prevent loss of work force due to illness. Rigorous testing of HCQ for this purpose is critical at this time. The investigators therefore aim to conduct the first randomized placebo-controlled trial of HCQ to prevent COVID-19 infections in emergency departments (ED) as they prepare for escalating rates of COVID-19 in Toronto, Canada.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||988 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||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.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||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.|
|Official Title:||Protecting Frontline Health Care Workers From COVID-19 With Hydroxychloroquine Pre-exposure Prophylaxis: A Randomized, Placebo-controlled Multi-Site Trial in Toronto, Canada|
|Actual Study Start Date :||April 30, 2020|
|Estimated Primary Completion Date :||August 27, 2020|
|Estimated Study Completion Date :||January 30, 2022|
Experimental: Study drug arm
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).
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.
Placebo Comparator: Placebo arm
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
Placebo pill (same formula as Hydroxychloroquine without active ingredient) taken once daily, for three months.
- Microbiologically confirmed COVID-19 (SARS-CoV-2 infection) [ Time Frame: Samples collected at day 0, 30, 60, 90 and 120 ]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).
- Adverse events [ Time Frame: Assessed at day 30, 60, 90, and day 120 ]Assessed using the DAIDS Table for Grading the Severity of Adverse Events
- Symptom duration of COVID-19 [ Time Frame: Collected every 7 days from day 7 to day 120 ]Collected weekly from participants via self-report, sent by email
- Days of hospitalization attributable to COVID-19 [ Time Frame: Collected every 7 days from day 7 to day 120 ]The number of days (or partial days) spent admitted to an acute care hospital during the study period
- Respiratory failure requiring ventilatory support attributable to COVID-19 [ Time Frame: Collected every 7 days from day 7 to day 120 ]the number of days (or partial days) requiring i) non-invasive and ii) endotracheal intubation with ventilation during the study period
- Mortality [ Time Frame: Collected every 7 days from day 7 to day 120 ]Mortality attributable to COVID-19 and all-cause mortality during the study period
- Impact on work eligibility [ Time Frame: Collected every 7 days from day 7 to day 120 ]Number of days ineligible/unable to work due to COVID-19
- Seropositivity [ Time Frame: Blood collected at day 0, 30, 60, 90, 120 ]COVID-19 reactive serology
- Short-term psychological impact [ Time Frame: Measured at day 1, 60, 120 ]Short-term psychological impact of exposure to COVID-19 measured using the K10, a validated measure of non-specific psychological distress, with a standard cutoff score of ≥16
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04374942
|University Health Network|
|Toronto, Ontario, Canada, M5G2C4|
|Principal Investigator:||Megan Landes, MD||University Health Network, Toronto|
|Principal Investigator:||Kevin Kain, MD||University Health Network, Toronto|