Clinical Trial Details
— Status: Terminated
Administrative data
NCT number |
NCT04374942 |
Other study ID # |
HEROs Protocol 1.5 |
Secondary ID |
ISRCTN14326006 |
Status |
Terminated |
Phase |
Phase 3
|
First received |
|
Last updated |
|
Start date |
April 30, 2020 |
Est. completion date |
March 31, 2021 |
Study information
Verified date |
April 2021 |
Source |
University Health Network, Toronto |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
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.