Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial.
OBJECTIVE
To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.


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


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


METHODS
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.


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


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
NCT00717093.
Smokers Information Centre, Fagerström Consulting AB, Berga Alle 1, 25452 Helsingborg, Sweden. Karl.fagerstrom@swipnet.se
Karl
K
Fagerström
Hans
H
Gilljam
Michael
M
Metcalfe
Serena
S
Tonstad
Michael
M
Messig
D000328:Adult; D001552:Benzazepines / Q000627:therapeutic use*; D003367:Cotinine / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011810:Quinoxalines / Q000627:therapeutic use*; D012008:Recurrence; D012463:Saliva / Q000737:chemistry; D020340:Tobacco Use Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000517:prevention & control*; D014030:Tobacco, Smokeless; D016896:Treatment Outcome; D000068580:Varenicline
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D003367:Cotinine; D000068580:Varenicline