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.