Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation - A randomized, double-blind, placebo-controlled trial

Background: Nicotine replacement therapy is an effective treatment for nico tine-dependent smokers. However, cessation rates are modest, and preliminar y studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler p lus placebo patch for smoking cessation. Methods A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group I (n = 200) received the nicotine inhaler plus nicotine patc h (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plu s placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then in haler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per da y ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentratio n less than 10 ppm. Results: Group I vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P=.02), 25.0% and 22.5% at 6 months (P=.56), and 19.5% and 14.0% at 12 months (P=.14). One-year sur vival analysis showed a significant association between abstinence and trea tment with nicotine inhaler plus nicotine patch (P=.04). Mean nicotine-subs titution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell si gnificantly and lung function showed a trend toward improvement. The most c ommon adverse events were throat irritation (inhaler) and itching (patch). Conclusions: Treatment with the nicotine inhaler plus nicotine patch result ed in significantly higher cessation rates than inhaler plus placebo patch.