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Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial

BMJ 2010; 341 doi: (Published 06 December 2010) Cite this as: BMJ 2010;341:c6549
  1. Karl Fagerström, director1,
  2. Hans Gilljam, professor2,
  3. Michael Metcalfe, senior medical manager3,
  4. Serena Tonstad, head consultant4,
  5. Michael Messig, primary care statistics5
  1. 1Smokers Information Centre, Fagerström Consulting AB, Berga Alle 1, 25452 Helsingborg, Sweden
  2. 2Department of Public Health Sciences, Karolinska Institutet, Postbox 17 070, 104 62 Stockholm, Sweden
  3. 3Pfizer, Tadworth, Surrey KT20 7NS, UK
  4. 4Oslo University Hospital, Ullevål Department of Preventive Cardiology, Oslo, Norway
  5. 5Pfizer, New York, NY 10017, USA
  1. Correspondence to: K Fagerström Karl.fagerstrom{at}
  • Accepted 17 September 2010


Objective To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.

Design Double blind, placebo controlled, parallel group, multicentre, randomised controlled trial.

Setting Medical clinics (mostly primary care) in Norway and Sweden.

Participants Men and women aged ≥18 who used smokeless tobacco at least eight times a day, with no abstinence period over three months within one year before screening, who wanted to quit all tobacco use. Participants were excluded if they used any other form of tobacco (except smokeless tobacco) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition.

Interventions Varenicline 1 mg twice daily (titrated during the first week) or placebo for 12 weeks, with 14 weeks’ follow-up after treatment.

Main outcome measures The primary end point was the four week continuous abstinence rate at the end of treatment (weeks 9-12) confirmed with cotinine concentration. A secondary end point was continuous abstinence rate for weeks 9-26. Safety and tolerability were also evaluated.

Results 431 participants (213 varenicline; 218 placebo) were randomised and received at least one dose of study drug. Participants’ demographics and baseline use of smokeless tobacco were similar (89% (189) and 90% (196), respectively, were men; mean age in both groups was 43.9; participants used smokeless tobacco products about 15 times a day, and about 80% first used smokeless tobacco within 30 minutes after awakening). Continuous abstinence rate at week 9-12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, P<0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9-26 was 45% (95) v 34% (73); relative risk 1.42, 1.08 to 1.79, P=0.012; risk difference 11%; number needed to treat 9). The most common adverse events in the varenicline group compared with the placebo group were nausea (35% (74) v 6% (14)), fatigue (10% (22) v 7% (15)), headache (10% (22) v 9% (20)), and sleep disorder (10% (22) v 7% (15)). Few adverse events led to discontinuation of treatment (9% (19) and 4% (9), respectively), and serious adverse events occurred in two (1%) and three (1%) participants, respectively.

Conclusion Varenicline can help people to give up smokeless tobacco and has an acceptable safety profile. The response rate in the placebo group in this study was high, suggesting a population less resistant to treatment than smokers.

Trial Registration NCT00717093.


  • We thank Abegale Templar, of UBC Scientific Solutions, for editorial assistance in the form of proof reading, collation of reviewers’ comments, formatting the manuscript for submission, preparation of figures and tables, and formatting of references. This editorial assistance was funded by Pfizer.

  • Contributors: KF and MMet participated in the design of the study. KF, ST, and HG participated in the collection of data. MMes was involved in data analysis. All authors were involved in interpretation of data, drafting the article, reviewing the article for important intellectual content, and the decision to submit the article for publication. KF, ST, and HG are independent from the funder of the study. All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. MMet is guarantor.

  • Funding: This work was supported by Pfizer. KF, HG, and ST did not receive any financial support with respect to the writing or development of this manuscript.

  • Role of the study sponsor: Pfizer, the study sponsor, was involved in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: the institutions of ST and HG received support from Pfizer for the clinical trial; KF, ST, and HG have specified relationships with Pfizer, who might have an interest in the submitted work; MMet and MMes are employees of, and stockholders in, Pfizer.

  • Ethical approval: This study was approved by the institutional review boards and independent ethics committees and all participants gave written informed consent.

  • Data sharing: No additional data available.

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