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.

Conflict of interest statement

Conflicts of Interest Statement: Dr. Lerman has served as a consultant to GlaxoSmithKline, one company that manufactures the nicotine patch. She has also served as a consultant or has received research funding from Astra Zeneca, Pfizer, and Novartis. Financial support for this study was not provided from an industry sponsor. Dr. Lerman had full access to the data and had full responsibility for the decision to submit for publication. No other author has additional conflicts of interest to disclose.

Figures

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; μR = 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.