Effects of Combined Varenicline With Nicotine Patch and of Extended Treatment Duration on Smoking Cessation: A Randomized Clinical Trial

Abstract

Importance: Smoking cessation medications are routinely used in health care. Research suggests that combining varenicline with the nicotine patch, extending the duration of varenicline treatment, or both, may increase cessation effectiveness.

Objective: To compare combinations of varenicline plus the nicotine or placebo patch vs combinations used for either 12 weeks (standard duration) or 24 weeks (extended duration).

Design, settings, and participants: Double-blind, 2 × 2 factorial randomized clinical trial conducted from November 11, 2017, to July 9, 2020, at 1 research clinic in Madison, Wisconsin, and at 1 clinic in Milwaukee, Wisconsin. Of the 5836 adults asked to participate in the study, 1251 who smoked 5 cigarettes/d or more were randomized.

Interventions: All participants received cessation counseling and were randomized to 1 of 4 medication groups: varenicline monotherapy for 12 weeks (n = 315), varenicline plus nicotine patch for 12 weeks (n = 314), varenicline monotherapy for 24 weeks (n = 311), or varenicline plus nicotine patch for 24 weeks (n = 311).

Main outcomes and measures: The primary outcome was carbon monoxide-confirmed self-reported 7-day point prevalence abstinence at 52 weeks.

Results: Among 1251 patients who were randomized (mean [SD] age, 49.1 [11.9] years; 675 [54.0%] women), 751 (60.0%) completed treatment and 881 (70.4%) provided final follow-up. For the primary outcome, there was no significant interaction between the 2 treatment factors of medication type and medication duration (odds ratio [OR], 1.03 [95% CI, 0.91 to 1.17]; P = .66). For patients randomized to 24-week vs 12-week treatment duration, the primary outcome occurred in 24.8% (154/622) vs 24.3% (153/629), respectively (risk difference, -0.4% [95% CI, -5.2% to 4.3%]; OR, 1.01 [95% CI, 0.89 to 1.15]). For patients randomized to varenicline combination therapy vs varenicline monotherapy, the primary outcome occurred in 24.3% (152/625) vs 24.8% (155/626), respectively (risk difference, 0.4% [95% CI, -4.3% to 5.2%]; OR, 0.99 [95% CI, 0.87 to 1.12]). Nausea occurrence ranged from 24.0% to 30.9% and insomnia occurrence ranged from 24.4% to 30.5% across the 4 groups.

Conclusions and relevance: Among adults smoking 5 cigarettes/d or more, there were no significant differences in 7-day point prevalence abstinence at 52 weeks among those treated with combined varenicline plus nicotine patch therapy vs varenicline monotherapy, or among those treated for 24 weeks vs 12 weeks. These findings do not support the use of combined therapy or of extended treatment duration.

Trial registration: ClinicalTrials.gov Identifier: NCT03176784.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Baker reported receiving personal fees from the National Cancer Institute for editing a monograph and grants from the National Cancer Institute. Dr Bolt reported receiving grants from the National Institutes of Health. Dr Fiore reported receiving personal fees from the National Cancer Institute. No other disclosures were reported.

Figures

Figure.. Participant Flow Diagram

aReceived treatment for schizophrenia or another psychotic disorder within past year. bFor stroke, myocardial infarction, congestive heart failure, or diabetes. cData collected through 52 weeks. dDid not complete the week 52 telephone assessment. These data include participants who withdrew from the study. eFor the primary outcome of self-reported 7-day point prevalence abstinence (biochemically confirmed as exhaled carbon monoxide level ≤5 ppm) at 52 weeks after target quit day, the analyses used the full sample randomized to the treatment groups (N = 1251) and assumed that missing observations reflected current smoking.