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

Abstract

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.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_discolsure.pdf (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.

Figures

Fig 1 Flow of participants through study

Fig 2 Continuous abstinence rates with varenicline versus placebo achieved at end of treatment. Continuous abstinence rates analysed with logistic regression models with terms for study centre and treatment group

Fig 3 Seven day point prevalence of abstinence for varenicline and placebo at end of treatment. Point prevalences of abstinence analysed with logistic regression models with terms for study centre and treatment group