Pre-Exposure Prophylaxis with Various Doses of Hdroxychloroquine among high-risk COVID 19 Healthcare Personnel: CHEER randomized controlled trial.

A Phase II, randomized, placebo-controlled clinical trial (Clinicaltrials.gov NCT04359537) was conducted at SZABMU/PIMS to evaluate the comparative efficacy of various HCQ doses in preventing COVID-19 among high-risk healthcare workers. Enrolment began on 1st May 2020, and the intervention continued for a total of 12 weeks.

A total of 228 participants were initially enrolled (Figure 1); of them, 28 were ineligible and excluded. Participants fulfilling the eligibility criteria were randomized into the four treatment groups. Group 1 participants (n=48) were intervened with HCQ 400 mg (locally manufactured by Getz Pharma) twice a day on day 1 followed by 400 mg weekly. Group 2 (n=51) participants were given HCQ 400 mg once every 3 weeks, group 3 (n=55) administered HCQ 200 mg once every 3 weeks and participants in the control group received placebo (n=46).

The baseline characteristics of all participants, including age, gender, role, comorbidities, and drug records, were obtained. COVID-19 related symptoms and adverse events (AEs) from the drug were self-reported by the enrolled participant during the study period. The COVID-19 exposure and preventive practices were monitored on a monthly basis. Disease severity was assessed through ordinal scale i.e. no illness (score=1), illness with outpatient observation (score=2), hospitalization (or post-hospital discharge) (score=3), hospitalization with ICU stay (score=4) and death from COVID 19 (score=5). All participants exhibiting COVID-19 symptoms were tested for SARS-CoV-2 during the study and also by the end of the 12th week, with PCR or IgM and IgG serology (as per accessibility).

The primary endpoint was to evaluate the COVID-19-free survival among the participants by the end of the study. The secondary endpoints were to evaluate the proportion of rRT-PCR positive COVID-19 cases, the role of exposure and preventive practices, the frequency of COVID-related symptoms, treatment-related side effects, the incidence of all-cause study medicine discontinuation, and maximum disease severity during the study treatment.

The study protocol was approved by the ethical review board of Shaheed Zulfiqar Ali Bhutto Medical University (Reference no. 1-1/2015/ERB/SZABMU/549; Dated 20 April 2020), and written informed consents were acquired from the participants before inclusion.