Chloroquine for influenza prevention: a randomised, double-blind, placebo
controlled trial.
Author(s): Paton NI, Lee L, Xu Y, Ooi EE, Cheung YB, Archuleta S, Wong G, Wilder-Smith A.
Affiliation(s): Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
nick.paton@ctu.mrc.ac.uk
Publication date & source: 2011, Lancet Infect Dis. , 11(9):677-83
BACKGROUND: Chloroquine has in-vitro activity against influenza and could be an
ideal candidate for worldwide prevention of influenza in the period between onset
of a pandemic with a virulent influenza strain and the development and widespread
dissemination of an effective vaccine. We aimed to assess the efficacy of such an
intervention.
METHODS: In this randomised, double-blind, placebo-controlled trial done at a
single centre in Singapore, we randomly assigned (1:1) healthy adults to receive
chloroquine phosphate (500 mg/day for 1 week, then once a week to complete 12
weeks) or matching placebo by use of a computer-generated randomisation list.
Participants filled an online symptom diary every week, supplemented by daily
diaries and self-administered nasal swabs when unwell.
Haemagglutination-inhibition assays for influenza A (H1N1, H3N2) and B were done
on blood samples taken at baseline and after 12 weeks. The primary outcome was
laboratory-confirmed clinical influenza defined by specific symptoms accompanied
by influenza RNA on nasal swabs or a four-fold increase in
haemagglutination-inhibition titres over the 12-week study period. Analysis was
by intention to treat. This trial was registered with ClinicalTrials.gov, number
NCT01078779.
FINDINGS: From November, 2009, to February, 2010, we recruited 1516 eligible
participants. 1496 (96%) returned at week 12 and were included in the efficacy
analysis. Adherence to study intervention was 97%, and 94% of the scheduled
weekly diaries were completed. Eight (1%) of 738 participants had
laboratory-confirmed clinical influenza in the placebo group and 12 (2%) of 724
in the chloroquine group (relative risk 1·53, 95% CI 0·63-3·72; p=0·376). 29 (4%)
of 738 had laboratory-confirmed influenza infection (symptomatic or asymptomatic)
in the placebo group and 38 (5%) of 724 in the chloroquine group (1·34,
0·83-2·14; p=0·261). 249 (33%) of 759 participants reported adverse events
(mostly mild) in the placebo group and 341 (45%) of 757 in chloroquine group
(p<0·0001). Headache, dizziness, nausea, diarrhoea, and blurred vision were more
common in the chloroquine group, but rarely resulted in treatment
discontinuation. One serious adverse event (hepatitis) was possibly related to
chloroquine.
INTERPRETATION: Although generally well tolerated by a healthy community
population, chloroquine does not prevent infection with influenza. Alternative
drugs are needed for large-scale prevention of influenza.
FUNDING: National Medical Research Council, Singapore.
Erratum in
Lancet Infect Dis. 2011 Sep;11(9):655. Smith, Annelies Wilder [corrected to
Wilder-Smith, Annelies].
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