Absence of evidence or evidence of absence - a review of the evidence for hydroxychloroquine as a potential candidate for prophylaxis against COVID-19

Clinical trials are investigating several agents as potential options for pre-exposure prophylaxis and post-exposure prophylaxis to prevent infection with COVID-19. A particular focus has been high risk groups including healthcare workers. Chloroquine (CQ) and hydroxychloroquine (HCQ) are the predominant agents in terms of numbers of clinical trials listed on Clinicaltrials.gov. However, CQ/HCQ have not been proven as an effective treatment option for COVID-19, and it is currently unclear what benefit, if any, is available to support their use in a prophylactic role. Four randomised control trials have been published so far which have examined the effect of HCQ as pre-exposure (PrEP) and post-exposure prophylaxis (PEP). This study summarises the evidence to date for HCQ as a potential prophylactic option for PEP and PrEP, presents both the aggregated and disaggregated data and details the gaps in the evidence base. The absolute risk differences for the pre-exposure prophylaxis studies were -0.3% to -2% and for the post prophylaxis studies were -0.6% and -2.4%. There were more adverse events noted in the hydroxychloroquine arms across all four studie