Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS CoV-2 in healthcare workers at high-risk of exposure. Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with Covid-19, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations. Results: We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18) and for twice weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19 (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08). Conclusions: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.

Hydroxychloroquine in COVID-19 Patients: Pros and Cons

“…In one double-blinded randomized clinical trial, the efficacy of HCQ in preventing COVID-19 was examined among 1,483 American and Canadian healthcare workers who are significantly exposed to COVID-19 patients in high-risk areas such as emergency departments, COVID-19 units and intensive care units (Rajasingham et al, 2020). The participants were assigned to three groups: 1) HCQ group 1, provided with a dose of 400 mg once weekly for 12 weeks, 2) HCQ group 2, provided with a dose of 800 mg twice weekly for 12 weeks, and 3) placebo group (Rajasingham et al, 2020). After 12 weeks of follow up, no significant difference in the incidence of COVID-19 was detected among the three groups (Rajasingham et al, 2020).…”

“…The participants were assigned to three groups: 1) HCQ group 1, provided with a dose of 400 mg once weekly for 12 weeks, 2) HCQ group 2, provided with a dose of 800 mg twice weekly for 12 weeks, and 3) placebo group (Rajasingham et al, 2020). After 12 weeks of follow up, no significant difference in the incidence of COVID-19 was detected among the three groups (Rajasingham et al, 2020). However, just like the previous study, this study was limited by the lack of adequate PCR testing, and also by the inherent error associated with the use of PCR in confirming COVID-19.…”

<p>Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19</p>

“…Because the studies were terminated prematurely they were underpowered to show a treatment benefit, however. 53,54 Since RCTs require an average of 5.5 years for completion at an average cost of over a million dollars, it may take a long time to obtain conclusive results from these studies. [55][56][57] In the face of a public health crisis, it is important to consider life-saving approaches based on scientific logic and clinical availability even if definitive results are pending.…”

Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review

“…The incidence of new COVID-19 did not differ between those receiving HCQ and placebo. Another trial with a similar design, investigating pre-exposure prophylaxis in HCW with once weekly or twice weekly HCQ, reported no protective benefit compared to placebo (Rajasingham et al, 2020). Both these trials had a pragmatic design, due to which certain limitations made it difficult to draw definite conclusions-only a few of the trial participants had an RT-PCR confirming their COVID-19 diagnoses, and the rest were labeled based on a symptom-based definition.…”