Postexposure prophylactic use of hydroxychloroquine not effective for Covid-19 prevention

1. Prophylactic use of hydroxychloroquine within four days after exposure did not decrease cumulative incidence of coronavirus disease 2019 (Covid-19).

2. No arrhythmias or deaths occurred in the hydroxychloroquine or placebo groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19). The rapid transmission and prevalence of the virus is accelerating the evaluation of existing medications to mitigate the infection such as hydroxychloroquine. Studies on the efficacy of hydroxychloroquine against Covid-19 focus on hospitalized patients with little consideration towards its preventative properties. As such, this study evaluated the potential for hydroxychloroquine to be used as postexposure prophylaxis to prevent symptomatic infection after Covid-19 exposure. The study determined the prophylaxis use of the medication did not prevent illness compatible with Covid-19 or confirmed infections compared to the placebo control group. This randomized trial was limited by the trial design, as it enrolled patients who were younger and healthier than the group at highest risk for severe Covid-19. The difference in the participant demographics may explain the lack of reported cardiac adverse events after hydroxychloroquine use. Nonetheless, this study was strengthened by the high medication adherence among trial participants.

Click to read the study in NEJM

Relevant Reading: Association of Treatment With Hydroxychloroquine or Azithromycin with In-Hospital Mortality in Patients With COVID-19 in New York State

In-Depth [randomized controlled trial]: This randomized control trial enrolled 821 patients in a multicenter study from Canada and the United States. Participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than six feet for more than 10 minutes were included in this study. Participants who were younger than 18 years of age and were hospitalized were excluded. The patients were randomized in a 1:1 ratio to receive hydroxychloroquine or placebo. The primary end point was symptomatic illness confirmed by a positive molecular assay or presence of Covid-19 related symptoms. Covid-19 related symptoms included presence of cough, shortness of breath, or difficulty breathing. During the 14-day follow-up, new Covid-19 cases were confirmed for 107 of 821 participants (13.0%).  Furthermore, there was no significant difference for the incidence of new illness compatible with Covid-19 between the participants administered hydroxychloroquine (49 of 414 [11.8%]) and those administered placebo (58 of 407 [14.3%]) (P=0.35). During the trial, two hospitalizations were reported, one in each group, and no participants experienced arrhythmias or death. Upon confirmation of Covid-19 diagnosis, the most common symptoms were fatigue (49.5%), cough (44.9%), fever (34.6%), and shortness of breath (18.7%). Confirmation of Covid-19 through symptom compatibility for the illness included 48 participants (11.6%) in the hydroxychloroquine group and 55 participants (13.5%) in the control group (P=0.46). Laboratory confirmation of Covid-19 was positive for 11 participants (2.7%) in the hydroxychloroquine group and 9 participants (2.2%) in the control group (P=0.82). Taken together, postexposure prophylactic use of hydroxychloroquine did not prevent the onset of Covid-19.

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