Timothy B Baker1,2, Megan E Piper1,2, Stevens S Smith1,2, Daniel M Bolt3, James H Stein4, Michael C Fiore1,2. 1. Center for Tobacco Research and Intervention, School of Medicine and Public Health, University of Wisconsin, Madison. 2. Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison. 3. Department of Educational Psychology, University of Wisconsin, Madison. 4. Division of Cardiovascular Medicine, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison.
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.
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.
Authors: A Eden Evins; Corinne Cather; Sarah A Pratt; Gladys N Pachas; Susanne S Hoeppner; Donald C Goff; Eric D Achtyes; David Ayer; David A Schoenfeld Journal: JAMA Date: 2014-01-08 Impact factor: 56.272
Authors: Jonathan Livingstone-Banks; Emma Norris; Jamie Hartmann-Boyce; Robert West; Martin Jarvis; Peter Hajek Journal: Cochrane Database Syst Rev Date: 2019-02-13
Authors: Robert A Schnoll; Patricia M Goelz; Anna Veluz-Wilkins; Sonja Blazekovic; Lindsay Powers; Frank T Leone; Peter Gariti; E Paul Wileyto; Brian Hitsman Journal: JAMA Intern Med Date: 2015-04 Impact factor: 21.873
Authors: Carrie D Patnode; Jillian T Henderson; Erin L Coppola; Joy Melnikow; Shauna Durbin; Rachel G Thomas Journal: JAMA Date: 2021-01-19 Impact factor: 56.272
Authors: Timothy B Baker; Megan E Piper; James H Stein; Stevens S Smith; Daniel M Bolt; David L Fraser; Michael C Fiore Journal: JAMA Date: 2016-01-26 Impact factor: 56.272
Authors: Tanya R Schlam; Michael C Fiore; Stevens S Smith; David Fraser; Daniel M Bolt; Linda M Collins; Robin Mermelstein; Megan E Piper; Jessica W Cook; Douglas E Jorenby; Wei-Yin Loh; Timothy B Baker Journal: Addiction Date: 2015-11-19 Impact factor: 6.526
Authors: Nicole L Nollen; Jasjit S Ahluwalia; Lisa Sanderson Cox; Kolawole Okuyemi; David Lawrence; Larry Samuels; Neal L Benowitz Journal: JAMA Netw Open Date: 2021-01-04
Authors: Harry Tattan-Birch; Loren Kock; Jamie Brown; Emma Beard; Linda Bauld; Robert West; Lion Shahab Journal: Nicotine Tob Res Date: 2022-06-23 Impact factor: 5.825