COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Primary Prevention Mitja O, Corbacho-Monne M, Ubals M, et al. A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19. N Engl J Med. 2021 Feb 4;384(5):417-427. doi: 10.1056/NEJMoa2021801. Epub 2020 Nov 24.
Abstract

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking.

METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days.

RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported.

CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).

Ratings
Discipline / Specialty Area Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Public Health
Infectious Disease
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Trials that confirm evidence of no benefit are important, so using the interventions can be ruled out. This study provides high-level evidence showing no benefit using hydroxychloroquine as prophylaxis in Covid-19 infection and that it has adverse effects.

Infectious Disease rater

This is a well-done trial that answers a question I suspect few people were waiting to learn after all the other negative results for this drug.

Infectious Disease rater

This is a well conducted study that echoes what is now broadly known: HCQ is not an effective treatment for COVID-19.

Public Health rater

The characteristics of the trial participants did not include patients with non-communicable diseases. This might be a confounding factor in the primary and secondary outcomes of the study. I would recommend assessing the outcome of hydoxychloroquine in patients having NCD and COVID-19.