Triple-combination pharmacotherapy for medically ill smokers: a randomized trial.

Background: Smokers with medical illnesses are at particular risk for complications caused by tobacco. Clinical trial data on the effectiveness of triple-combination pharmacotherapy for tobacco dependence treatment in these high-risk smokers are not available.

Objective: To evaluate extended duration of a triple-medication combination versus standard-duration therapy with the nicotine patch alone and 6-month abstinence rates in smokers with medical illnesses.

Design: Randomized clinical trial from 2005 to 2007.

Setting: Single primary care setting.

Patients: 127 smokers 18 years or older with predefined medical illnesses were recruited from the local community.

Intervention: Participants were allocated by blocked randomization to receive either the nicotine patch alone for a standard 10-week, tapering course (n = 64) or the combination of nicotine patch, nicotine oral inhaler, and bupropion ad libitum (n = 63). Nonstudy staff, who used computer-generated tables, assigned participants by telephone. No study staff had access to the randomization tables before randomization, thus maintaining concealment. Participants and study personnel were not blinded to treatment assignment.

Measurements: The primary outcome was 7-day, exhaled carbon monoxide-confirmed point abstinence at 26 weeks after target quit date. Secondary outcomes were the time to first relapse, duration of medication use, and adverse effects of medications. Analyses were conducted on an intention-to-treat basis with participants who were lost to follow-up (patch alone [n = 13] and combination therapy [n = 18]) classified as still smoking.

Results: Both treatment groups had similar baseline characteristics. Abstinence rates at 26 weeks were 35% (22 of 63 patients) for the combination group versus 19% (12 of 64 patients) for the patch-alone group (relapse benefit, 16% [95% CI, 1% to 31%]; P = 0.040). The adjusted odds ratio for abstinence in the combination group was 2.57 (CI, 1.05 to 6.32; P = 0.041). The median time to relapse was significantly longer in the combination group than in the patch-alone group (65 days vs. 23 days; P = 0.005). Some side effects occurred more frequently in the combination group (for example, insomnia [25% vs. 9%] and anxiety [22% vs. 3%]), but the proportion of participants who discontinued study medications because of adverse events was similar in both groups (6%).

Limitations: Approximately 25% of participants were lost to follow-up (proportions were similar between treatment groups). Treatment personnel and participants were unblinded.

Conclusion: Flexibly dosed triple-combination pharmacotherapy for up to 6 months was more effective than standard-duration nicotine patch therapy for outpatient smokers with medical illnesses.

Primary Funding Source: Cancer Institute of New Jersey and Robert Wood Johnson Foundation.