HCQ for Primary Prophylaxis Against COVID19 in Health-care Workers
Status:
Not yet recruiting
Trial end date:
2020-08-01
Target enrollment:
Participant gender:
Summary
Background:
Aim: To demonstrate the efficacy of low-dose hydroxychloroquine as primary prevention in
healthcare workers Design, participants and interventions: Prospective, randomized, parallel
group, double-blinded, placebo controlled, study.
including 440 participants who will be randomised to 2 treatment arms: hydroxychloroquine or
placebo.
Outcome variables: symptomatic or asymptomatic SARS-CoV-2 infection confirmed by PCR, viral
load during SARS-CoV-2 infection, seroconversion during the study period, incidence of any
acute respiratory infection, days of sick leave.
Statistical considerations: No trials have been published investigating the efficacy of HCQ
as primary prophylaxis of SARS-CoV-2 infection in health care workers. Thus, sample size
calculations in the proposed trial are based on the investigators' best estimates for several
parameters.
In accordance to the effect of oseltamivir against symptomatic influenza, we assumed an
approximate effectiveness of approximately 60% (HR of 0.4)
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464969/) as realistic. As a prophylactic
intervention with HCQ, which may have side effects and for which supply shortage can be
expected, was judged justifiable only if its effectiveness is high, we based our sample size
consideration on a HR of 0.3. To estimate the probability of an event in both the
experimental and the control group, very little data is available. In a Dutch
point-prevalence study 0-10% of health-care workers were infected depending on the healthcare
institution, depending on the hospital. This point-prevalence study was performed between 6
and 9 March, when the reported number of cases in the Netherlands was 33 and 77,
respectively, according to the RIVM
(https://www.rivm.nl/nieuws/resultaat-steekproef-4-ziekenhuismedewerkers-heeft-coronavirus).
Additionally, in an a report published in the Lancet, 20% of responding healthcare workers in
Italy were found to be infected with SARS-CoV2 within less than one month
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30627-9/fulltext).
Several media reports indicate that this proportion is similar across various healthcare
institutions and countries
(https://www.nytimes.com/2020/03/24/world/europe/coronavirus-europe-covid-19.html) and
(https://www.aljazeera.com/news/2020/03/spain-tightens-restrictions-week-lockdown-begins-2003
30191539568.html).
As the proposed study will be performed in a high-risk setting, we assumed an event (i.e. PCR
positivity) probability of 10% in the control group and 3% in the experimental arm after the
maximum study period. In summary, a sample size of 210 participants per arm is necessary to
detect a HR of 0.3 with a power of 80.3% with an alpha-error of 0.05. To account for
drop-outs and asymptomatic, undetected infection at inclusion or past infection with existing
immunity, an additional 10 participants will randomized per treatment arm. The overall study
population is therefore 440 participants.
Statistical analysis will be based on two populations: A Modified Intention to Treat
population excluding those who withdrew consent after randomization and those with a positive
serology at baseline. And a per protocol population including all randomized subjects who
completed at least 3 out of 4 follow-up visits and took at least 80% of all doses of study
medication.