In this episode, I’ll discuss an article about hydroxychloroquine for prophylaxis after high-risk Covid-19 exposure.
Lead author: David R. Boulware
Published in: New England Journal of Medicine June 2020
With in vitro data suggesting that hydroxychloroquine has activity against Covid-19, there is as much interest in using it as preventative therapy as there is for treatment. The authors of this trial sought to determine whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure.
Because observational studies have both suggested benefits of hydroxychloroquine as well as mixed results, the author chose a randomized double-blind placebo-controlled trial design.
Recruitment for this trial was done extensively over social media, and it was very popular among health care professionals. Participants could self-report a high-risk exposure to someone with confirmed Covid-19 at a distance of fewer than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk) or while wearing a face mask but no eye shield (moderate-risk). Study medication or placebo was then shipped overnight in the US and Canada as long as the patient would be able to start within 4 days of exposure.
The hydroxychloroquine regimen used was 800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days.
The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.
821 asymptomatic patients were enrolled. Nearly 90% reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between groups with 11.8% of those receiving hydroxychloroquine and 14.3% those receiving placebo reporting Covid-19 compatible illness. The hydroxychloroquine group had more mild side effects than placebo (40.1% vs. 16.8%), but no group reported a serious adverse reaction.
The authors concluded:
After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure
This trial was novel in design with its heavy focus on recruiting via social media. The median age of patients was 40 years and only about one-quarter of patients had a chronic health condition. Two-thirds of the patients were healthcare workers who were exposed either by patients or coworkers.
Unfortunately, the limitations of the study leaves open the question of whether hydroxychloroquine has the potential to prevent Covid-19. Because diagnostic testing was not widely available, and because the participants were spread out across North America and not able to come to a study testing site, only Covid-19-like symptoms could be measured.
In addition, the study group of relatively young and healthy patients is not necessarily representative of the group of patients that would most likely benefit from prophylaxis.
An accompanying editorial to this study points out that 60 additional studies of hydroxychloroquine are registered, and that
The results reported by Boulware et al. are more provocative than definitive, suggesting that the potential prevention benefits of hydroxychloroquine remain to be determined.
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