Remote post-exposure prophylaxis RCT reporting "[HCQ] did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure".
However, this statement is incorrect - cases were reduced, just without statistical significance - it's not possible to conclude there was no efficacy. Additionally, treatment was not within 4 days - there was up to 68 hours shipping delay as below.
Further, 6 independent analyses of the data in this study indicate efficacy:
arxiv.org, blog.philbirnbaum.com, drive.google.com, longdom.org, medrxiv.org, osf.io, researchgate.net.
COVID-19 cases were reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at
p=0.002. For more detailed analysis, see
c19hcq.org.
See also:
nejm.org. Regarding the use of folic acid, see
sciencedirect.com.
Time of dosing was not recorded in these trials:
osf.io (B). See
medrxiv.org (B), and Pullen et al.
ncbi.nlm.nih.gov, which shows shipping delay for these trials of 19 - 68 hours. With enrollment up to 4 days from exposure, this implies delivery 19 - 164 hours after exposure.
risk of case, 17.0% lower, RR 0.83, p = 0.35, treatment 49 of 414 (11.8%), control 58 of 407 (14.3%), NNT 41.
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risk of case, 25.1% lower, RR 0.75, p = 0.22, treatment 32 of 414 (7.7%), control 42 of 407 (10.3%), NNT 39, probable COVID-19 cases.
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Boulware et al., 3 Jun 2020, Randomized Controlled Trial, USA, peer-reviewed, 24 authors, study period 17 March, 2020 - 6 May, 2020, this trial compares with another treatment - results may be better when compared to placebo.
A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
David R Boulware, Matthew F Pullen, Ananta S Bangdiwala, Katelyn A Pastick, Sarah M Lofgren, Elizabeth C Okafor, Caleb P Skipper, Alanna A Nascene, Melanie R Nicol, Mahsa Abassi, Nicole W Engen, Matthew P Cheng, Derek Labar, Sylvain A Lother, Lauren J Mackenzie, Glen Drobot, Nicole Marten, Ryan Zarychanski, Lauren E Kelly, Ilan S Schwartz, Emily G Mcdonald, Radha Rajasingham, Todd C Lee, Kathy H Hullsiek
New England Journal of Medicine, doi:10.1056/nejmoa2016638
BACKGROUND Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.
METHODS We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (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.
RESULTS We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) 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 participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P = 0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.
CONCLUSIONS 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. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.
n engl j med nejm.org
8 T h e ne w e ngl a nd jou r na l o f m e dicine exposure prophylaxis would be effective in highrisk populations is a separate question, with trials ongoing. In order to end the pandemic, a reduction in community transmission is needed. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the participants who consented to participate in this randomized trial; the members of the data and safety monitoring board (Drs. George Thompson III, Andrej Spec, Tom Chiller, and Bozena Morawski) for their thoughtful, generous service; and Drs. Jakub Tolar, Alexis Turgeon, Brad Benson, Tim Schacker, and Peter Igarashi for institutional support. Dr. Boulware thanks Drs. Paul Bohjanen and Ed Janoff for their mentorship. * Values are through day 5, the date of the scheduled completion of the trial intervention. More than one side effect could occur. Ongoing side effects were reported by approximately 3% of the participants in the hydroxychloroquine group at days 10 and 14 and by less than 1% of those in the placebo group. There was no association between the occurrence of side effects and the incidence of Covid-19. Among participants in whom Covid-19 developed, 30.0% (30 of 100) reported a side effect, as compared with 28.2% (169 of 600) reporting a side effect in whom Covid-19 did not develop (P =..