Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial

Abstract

Background: Tobacco dependence is a chronic, relapsing condition that may require extended treatment.

Objective: To assess whether extended-duration transdermal nicotine therapy increases abstinence from tobacco more than standard-duration therapy in adult smokers.

Design: Parallel randomized, placebo-controlled trial from September 2004 to February 2008. Participants and all research personnel except the database manager were blinded to randomization. (ClinicalTrials.gov registration number: NCT00364156)

Setting: Academic center.

Participants: 568 adult smokers.

Intervention: In an unstratified small block-randomization scheme, participants were randomly assigned to standard therapy (Nicoderm CQ [GlaxoSmithKline, Research Triangle Park, North Carolina], 21 mg, for 8 weeks and placebo for 16 weeks) or extended therapy (Nicoderm CQ, 21 mg, for 24 weeks).

Measurements: The primary outcome was biochemically confirmed point-prevalence abstinence at weeks 24 and 52. Secondary outcomes were continuous and prolonged abstinence, lapse and recovery events, cost per additional quitter, and side effects and adherence.

Results: At week 24, extended therapy produced higher rates of point-prevalence abstinence (31.6% vs. 20.3%; odds ratio, 1.81 [95% CI, 1.23 to 2.66]; P = 0.002), prolonged abstinence (41.5% vs. 26.9%; odds ratio, 1.97 [CI, 1.38 to 2.82]; P = 0.001), and continuous abstinence (19.2% vs. 12.6%; odds ratio, 1.64 [CI, 1.04 to 2.60]; P = 0.032) versus standard therapy. Extended therapy reduced the risk for lapse (hazard ratio, 0.77 [CI, 0.63 to 0.95]; P = 0.013) and increased the chances of recovery from lapses (hazard ratio, 1.47 [CI, 1.17 to 1.84]; P = 0.001). Time to relapse was slower with extended versus standard therapy (hazard ratio, 0.50 [CI, 0.35 to 0.73]; P < 0.001). At week 52, extended therapy produced higher quit rates for prolonged abstinence only (P = 0.027). No differences in side effects and adverse events between groups were found at the extended-treatment assessment.

Limitation: The generalizability of the findings may be limited because participants were smokers without medical comorbid conditions who were seeking treatment, and differences in adherence across treatment groups were detected.

Conclusion: Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy.

Primary funding source: National Institutes of Health.

Figure 1. Participant Flow

Note. * A list of the reasons for participant ineligibility can be provided by the authors upon request; inclusion and exclusion criteria listed in the text were identical for phone and in-person eligibility assessments; ** indicates included in intent-to-treat analysis.

Figure 2. Time to Relapse by Treatment Arm to Week 52

Note. HR = Hazard Ratio (with 95% CI); n = number of participants at risk for relapse; μ_R = restricted mean number of weeks to relapse (included censored observation times); the model controled for age (HR = 1.00, 95% CI: 0.99-1.01, p = 0.65), sex (HR = 0.96, 95% CI: 0.77-1.19, p = 0.69), and level of nicotine dependence. Nicotine dependence level predicted relapse from 0 to 8 weeks (HR = 1.83, 95% CI: 1.35-2.48, p < 0.001), but not from weeks 9-24 (HR = 0.91, 95% CI: 0.61-1.36, p = 0.65), or weeks 25-52 (HR = 1.04, 95% CI: 0.60-1.70, p = 0.90). The HRs were stable and uniform over the time intervals (p = 0.80). There is a residual decline in abstinence after 24 weeks, but the decline is statistically equivalent across treatment arms.