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.

中文翻译：

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伐尼克兰联合尼古丁贴剂和延长治疗时间对戒烟的影响：一项随机临床试验。

重要性 戒烟药物通常用于医疗保健。研究表明，将伐尼克兰与尼古丁贴片结合使用、延长伐尼克兰治疗的持续时间或两者兼而有之，可能会提高戒烟效果。目的比较伐尼克兰加尼古丁或安慰剂贴片的组合与使用 12 周（标准持续时间）或 24 周（延长持续时间）的组合。设计、设置和参与者 2017 年 11 月 11 日至 2020 年 7 月 9 日在威斯康星州麦迪逊的 1 个研究诊所和威斯康星州密尔沃基的 1 个诊所进行的双盲、2 × 2 因子随机临床试验。在被要求参加这项研究的 5836 名成年人中，1251 名每天吸烟 5 支或以上的人被随机分配。干预 所有参与者都接受了戒烟咨询，并被随机分配到 4 个药物组中的 1 个：伐尼克兰单药治疗 12 周（n = 315），伐尼克兰加尼古丁贴片 12 周（n = 314），伐尼克兰单药治疗 24 周（n = 311） ，或伐尼克兰加尼古丁贴剂 24 周（n = 311）。主要结果和测量 主要结果是在 52 周时一氧化碳确认的自我报告的 7 天点戒断率。结果 在随机分组的 1251 名患者中（平均 [SD] 年龄，49.1 [11.9] 岁；675 [54.0%] 名女性），751 (60.0%) 名完成了治疗，881 (70.4%) 名提供了最终随访。对于主要结局，药物类型和用药持续时间这两个治疗因素之间没有显着的交互作用（优势比 [OR]，1.03 [95% CI，0.91 至 1.17]；P = .66）。对于随机分配至 24 周和 12 周治疗持续时间的患者，主要结局分别发生在 24.8% (154/622) 和 24.3% (153/629)（风险差异，-0.4% [95% CI，-5.2 % 至 4.3%]；或，1.01 [95% CI，0.89 至 1.15]）。对于随机接受伐尼克兰联合治疗与伐尼克兰单药治疗的患者，主要结局分别为 24.3% (152/625) 和 24.8% (155/626)（风险差异，0.4% [95% CI，-4.3% 至 5.2% ]；或，0.99 [95% CI，0.87 至 1.12]）。4 组的恶心发生率为 24.0% 至 30.9%，失眠发生率为 24.4% 至 30.5%。结论和相关性 在每天吸烟 5 支或以上的成年人中，伐尼克兰联合尼古丁贴片治疗与伐尼克兰单药治疗的 52 周时 7 天点戒烟率无显着差异，或在接受 24 周与 12 周治疗的患者中。这些发现不支持使用联合治疗或延长治疗时间。试验注册 ClinicalTrials.gov 标识符：NCT03176784。