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Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial.
Lancet Infect Dis. 2011 Sep; 11(9):677-83.LI

Abstract

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.

Authors+Show Affiliations

Yong Loo Lin School of Medicine, National University of Singapore, Singapore. nick.paton@ctu.mrc.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21550310

Citation

Paton, Nicholas I., et al. "Chloroquine for Influenza Prevention: a Randomised, Double-blind, Placebo Controlled Trial." The Lancet. Infectious Diseases, vol. 11, no. 9, 2011, pp. 677-83.
Paton NI, Lee L, Xu Y, et al. Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. Lancet Infect Dis. 2011;11(9):677-83.
Paton, N. I., Lee, L., Xu, Y., Ooi, E. E., Cheung, Y. B., Archuleta, S., Wong, G., Wilder-Smith, A., & Smith, A. W. (2011). Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. The Lancet. Infectious Diseases, 11(9), 677-83. https://doi.org/10.1016/S1473-3099(11)70065-2
Paton NI, et al. Chloroquine for Influenza Prevention: a Randomised, Double-blind, Placebo Controlled Trial. Lancet Infect Dis. 2011;11(9):677-83. PubMed PMID: 21550310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. AU - Paton,Nicholas I, AU - Lee,Lawrence, AU - Xu,Ying, AU - Ooi,Eng Eong, AU - Cheung,Yin Bun, AU - Archuleta,Sophia, AU - Wong,Gerard, AU - Wilder-Smith,Annelies, AU - Smith,Annelies Wilder, Y1 - 2011/05/05/ PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2011/10/25/medline SP - 677 EP - 83 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 11 IS - 9 N2 - 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. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/21550310/Chloroquine_for_influenza_prevention:_a_randomised_double_blind_placebo_controlled_trial_ DB - PRIME DP - Unbound Medicine ER -