Randomized Comparison of a Nicotine Inhaler and Bupropion for Smoking Cessation and Relapse Prevention

doi:10.4065/82.2.186

Mayo Clinic Proceedings

Volume 82, Issue 2, February 2007, Pages 186-195

https://doi.org/10.4065/82.2.186 Get rights and content

OBJECTIVE

To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention.

METHODS

Smokers were randomized to receive a nicotine inhaler, bupropion, or both for 3 months. At 3 months, smoking-abstinent study participants were randomized to their initial medications or placebo. Participants who were smoking at 3 months were randomized to an alternative treatment regimen or placebo. This study was conducted from July 2001 to January 2003.

RESULTS

A total of 1700 smokers were randomized to treatment (phase 1) for 3 months. Among the 941 study participants eligible for randomization to the phase 2 trial, 837 continued in the study. For the phase 2 trial, 405 smoking-abstinent participants were randomized to relapse prevention for 9 additional months, and 432 smokers were randomized to re-treatment for an additional 3 months. At the end of the initial 3 months of treatment (phase 1), 82 (14%) of 566, 145 (26%) of 567, and 194 (34%) of 567 study participants receiving a nicotine inhaler, bupropion, or both, respectively, were abstinent from smoking. Of the 405 smoking-abstinent participants at the end of 3 months, the bupropion group had more smokers than the placebo group (mean No. of smokers, 1.5 vs 1.1; P<.001), and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group. Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention, but this difference disappeared after the initial 3 months. Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen, the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo (8 [7%] of 111 vs 0 [0%] of 112; P=.003), and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates (6 [6%] of 104 vs 3 [3%] of 105; P=.50).

CONCLUSION

Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates. Continuation of the initial combination therapy does not appear to prevent relapse to smoking. Timing of re-treatment and alternative approaches to relapse prevention should be further examined.

Section snippets

Study Design

This multicenter, randomized clinical trial included 3 sequential phases: open label (phase 1), placebo controlled (phase 2), and follow-up (phase 3). We conducted this study through the North Central Cancer Treatment Group (NCCTG), a large cooperative group of oncology practices throughout the United States that performs multiple chemotherapeutic clinical trials in oncology patients. Because these investigative sites do not specialize in treating tobacco dependence, they could be viewed as

RESULTS

Among the 19 sites participating in this study, 1708 individuals were eligible to be enrolled. Of these, 8 were excluded from the study: 6 cancelled before study enrollment, 1 was ineligible at time of enrollment, and 1 was a major protocol violation. This resulted in 1700 individuals being randomized to treatment (phase 1) for 3 months. Among the 941 participants eligible for rerandomization to phase 2, 837 continued in the study, 27 were subsequently randomized but were misclassified and

DISCUSSION

This is the first study, to our knowledge, to compare the combination of a nicotine inhaler and bupropion to each treatment alone. Whereas the smoking abstinence rates for the nicotine inhaler and bupropion alone groups are consistent with those reported in the literature,5, 6, 17, 18, 19, 20, 21 study participants who received the combination of bupropion and a nicotine inhaler had significantly higher smoking abstinence rates compared with those assigned to either treatment alone. Thus,

CONCLUSION

Combination therapy with bupropion and a nicotine inhaler appears to be efficacious for initiating abstinence in persons who are trying to stop smoking. However, continuation of combination therapy for more than 3 months does not appear to prevent relapse. Immediate re-treatment after initial treatment failure does not appear to be effective, but re-treatment after initial treatment failure should not be abandoned. Rather, more research is needed to investigate the most appropriate and

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Pharmacotherapy trials for treating tobacco dependence would benefit from behavioral interventions providing treatment consistent with clinical practice guidelines but not directing participants to treatments not evaluated in the trial. The Smoke Free and Living It© behavioral intervention manual includes participant and interventionist guides and is designed to provide both practical counseling and intra-treatment support. We utilized this intervention manual in a multicenter, randomized clinical trial of smokers with attention deficit hyperactivity disorder. In this study, we evaluated how the interventional manual performed in a “train-the-trainer” model requiring uniform counseling across 6 sites and 15 interventionists. We analyzed the skill-adherence of the interventionists and the intervention-adherence of the participants. The 255 randomized participants completed 9.3 ± 2.8 sessions (mean ± SD), with 157 participants (61.6%) completing all 11 of the sessions and 221 (86.7%) completing at least 6 of the 11 sessions. Of the 163 sessions for which the study interventionists were evaluated, 156 (95.7%) were rated as adherent to protocol and “meeting expectations” on at least 6 of 7 established criteria, illustrating that fidelity can be maintained with minimal supervision. The self-help and interventionists guides of the Smoke Free and Living It manual can thus be used to provide behavioral intervention with a high rate of adherence by both the interventionists and the participants. This manual meets the requirements of the United States Public Health Service Clinical Practice Guideline, can be adapted to specific research protocols, and provides a useful option for behavioral intervention during clinical trials for smoking cessation.
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View all citing articles on Scopus

: This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA25224, CA37404, CA15083, CA63826, CA35195, CA35448, CA35431, CA35101, CA35113, CA35103, CA52352, and CA63848.

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ORIGINAL ARTICLERandomized Comparison of a Nicotine Inhaler and Bupropion for Smoking Cessation and Relapse Prevention

OBJECTIVE

METHODS

RESULTS

CONCLUSION

Section snippets

Study Design

RESULTS

DISCUSSION

CONCLUSION

Lancet

Addic Behav

Chest

Actual causes of death in the United States, 2000 [published corrections appear in JAMA 2005;293:293-294 and 298]

JAMA

Treating Tobacco Use and Dependence: Clinical Practice Guideline

Efficacy of the nicotine inhaler as an adjunct to smoking cessation

Am J Health Behav

Efficacy of a nicotine inhaler in smoking cessation: a double-blind, placebo-controlled trial

Addiction

A comparison of sustained-release bupropion and placebo or smoking cessation

N Engl J Med

A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation

N Engl J Med

Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial

Arch Intern Med

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation

J Intern Med

Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study

Eur Heart J

The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire

Br J Addict

ORIGINAL ARTICLE
Randomized Comparison of a Nicotine Inhaler and Bupropion for Smoking Cessation and Relapse Prevention