N Engl J Med A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

[tetano]

N Engl J Med


. 2020 Jun 3.
doi: 10.1056/NEJMoa2016638. Online ahead of print.
A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19


David R Boulware[SUP] 1 [/SUP], Matthew F Pullen[SUP] 1 [/SUP], Ananta S Bangdiwala[SUP] 1 [/SUP], Katelyn A Pastick[SUP] 1 [/SUP], Sarah M Lofgren[SUP] 1 [/SUP], Elizabeth C Okafor[SUP] 1 [/SUP], Caleb P Skipper[SUP] 1 [/SUP], Alanna A Nascene[SUP] 1 [/SUP], Melanie R Nicol[SUP] 1 [/SUP], Mahsa Abassi[SUP] 1 [/SUP], Nicole W Engen[SUP] 1 [/SUP], Matthew P Cheng[SUP] 1 [/SUP], Derek LaBar[SUP] 1 [/SUP], Sylvain A Lother[SUP] 1 [/SUP], Lauren J MacKenzie[SUP] 1 [/SUP], Glen Drobot[SUP] 1 [/SUP], Nicole Marten[SUP] 1 [/SUP], Ryan Zarychanski[SUP] 1 [/SUP], Lauren E Kelly[SUP] 1 [/SUP], Ilan S Schwartz[SUP] 1 [/SUP], Emily G McDonald[SUP] 1 [/SUP], Radha Rajasingham[SUP] 1 [/SUP], Todd C Lee[SUP] 1 [/SUP], Kathy H Hullsiek[SUP] 1 [/SUP]



Affiliations

• PMID: 32492293
• DOI: 10.1056/NEJMoa2016638

Abstract

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.).

 

[Emily]

I don't think folic acid should have been chosen as a placebo unless someone wanted to make hydroxychloroquine look less effective than it is, or you wanted to examine folic acid as a prophylactic. They still should have had a control group that either didn't take any pills or that used a real placebo.

https://www.startribune.com/anti-mal...-19/570989342/
"Results published online Wednesday by the New England Journal of Medicine showed little difference in the onset of COVID-19 in 414 people who took hydroxychloroquine and a comparison group of 407 that took only folic acid vitamins. All participants had at least moderate risk for COVID-19 after being exposed to others in their homes or workplaces who had the illness.

There was a small difference, as 11.8% of people taking the drug developed COVID-19, compared with 14.3% of those taking vitamins, the study showed. However, that difference was considered statistically insignificant."

This is a placebo??? They were given multiple tablets per day with a loading dose the first day. Couldn't find the cummulative dose, but I expect it to be high.
https://arxiv.org/abs/2004.08920

[Submitted on 19 Apr 2020]
Hispidin and Lepidine E: two Natural Compounds and Folic acid as Potential Inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study


Talia Serseg, Khedidja Benarous, Mohamed Yousfi

2019-nCoV is a novel coronavirus was isolated and identified in 2019 in Wuhan, China. On 17th February and according to world health organization, a number of 71 429 confirmed cases worldwide, among them 2162 new cases recorded in the last 24 hours. There is no drug or vaccine for human and animal coronavirus. The inhibition of 3CL hydrolase enzyme provides a promising therapeutic principle for developing treatments against CoViD-19. The 3CLpro (Mpro) known for involving in counteracting the host innate immune response. This work presents the inhibitory effect of some natural compounds against 3CL hydrolase enzyme, and explain the main interactions in inhibitor-enzyme complex. Molecular docking study carried out using Autodock Vina. By screening several molecules, we identified three candidate agents that inhibit the main protease of coronavirus. Hispidin, lepidine E, and folic acid bound tightly in the enzyme, strong hydrogen bonds have been formed (1.69-1.80&[Aring]) with the active site residues. This study provides a possible therapeutic strategy for CoViD-19.​

[TD="class: tablecell label"]Subjects:[/TD]
[TD="class: tablecell subjects"]Biomolecules (q-bio.BM); Tissues and Organs (q-bio.TO)[/TD]

[TD="class: tablecell label"]Cite as:[/TD]
[TD="class: tablecell arxivid"] arXiv:2004.08920 [q-bio.BM][/TD]

[TD="class: tablecell label"] [/TD]
[TD="class: tablecell arxividv"](or arXiv:2004.08920v1 [q-bio.BM] for this version)[/TD]