Stellenbosch University, Cape Town, South Africa.
University of Cape Town, Cape Town, South Africa.
JAMA. 2014 Jul;312(2):155-61. doi: 10.1001/jama.2014.7195.
Behavioral approaches and pharmacotherapy are of proven benefit in assisting smokers to quit, but it is unclear whether combining nicotine replacement therapy (NRT) with varenicline to improve abstinence is effective and safe.
To evaluate the efficacy and safety of combining varenicline and a nicotine patch vs varenicline alone in smoking cessation.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and a further 12-week follow-up conducted in 7 centers in South Africa from April 2011 to October 2012. Four hundred forty-six generally healthy smokers were randomized (1:1); 435 were included in the efficacy and safety analyses.
Nicotine or placebo patch treatment began 2 weeks before a target quit date (TQD) and continued for a further 12 weeks. Varenicline was begun 1 week prior to TQD, continued for a further 12 weeks, and tapered off during week 13.
Tobacco abstinence was established and confirmed by exhaled carbon monoxide measurements at TQD and at intervals thereafter up to 24 weeks. The primary end point was the 4-week exhaled carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 of treatment, ie, the proportion of participants able to maintain complete abstinence from smoking for the last 4 weeks of treatment, as assessed using multiple imputation analysis. Secondary end points included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9 through 24, and adverse events. Multiple imputation also was used to address loss to follow-up.
The combination treatment was associated with a higher continuous abstinence rate at 12 weeks (55.4% vs 40.9%; odds ratio [OR], 1.85; 95% CI, 1.19-2.89; P = .007) and 24 weeks (49.0% vs 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) and point prevalence abstinence rate at 6 months (65.1% vs 46.7%; OR, 2.13; 95% CI, 1.32-3.43; P = .002). In the combination treatment group, there was a numerically greater incidence of nausea, sleep disturbance, skin reactions, constipation, and depression, with only skin reactions reaching statistical significance (14.4% vs 7.8%; P = .03); the varenicline-alone group experienced more abnormal dreams and headaches.
Varenicline in combination with NRT was more effective than varenicline alone at achieving tobacco abstinence at 12 weeks (end of treatment) and at 6 months. Further studies are needed to assess long-term efficacy and safety.
clinicaltrials.gov Identifier: NCT01444131.
行为方法和药物治疗在帮助吸烟者戒烟方面已被证明是有效的，但尚不清楚联合使用尼古丁替代疗法（NRT）和伐尼克兰是否能提高戒烟的效果和安全性。
评估尼古丁贴片联合伐尼克兰与单独使用伐尼克兰在戒烟方面的疗效和安全性。
设计、地点和参与者：这是一项随机、双盲、安慰剂对照的临床试验，在南非的 7 个中心进行，治疗期为 12 周，进一步的随访期为 12 周。2011 年 4 月至 2012 年 10 月，共招募了 446 名一般健康的吸烟者，按 1:1 随机分组；435 名被纳入疗效和安全性分析。
尼古丁或安慰剂贴片治疗在目标戒烟日（TQD）前 2 周开始，并持续 12 周。伐尼克兰在 TQD 前 1 周开始，持续 12 周，并在第 13 周逐渐减少剂量。
通过 TQD 时呼出的一氧化碳测量和之后的 24 周内的时间点来确定烟草的戒断情况，并确认其有效性。主要终点是治疗第 9 至 12 周时的 4 周呼出的一氧化碳确认的连续戒烟率，即通过多重插补分析评估参与者在治疗的最后 4 周内保持完全戒烟的比例。次要终点包括 6 个月时的点患病率戒断率、治疗第 9 至 24 周的连续戒烟率以及不良反应。多重插补也用于解决失访问题。
联合治疗在 12 周（55.4% vs 40.9%；优势比[OR]，1.85；95%置信区间[CI]，1.19-2.89；P=0.007）和 24 周（49.0% vs 32.6%；OR，1.98；95% CI，1.25-3.14；P=0.004）时的连续戒烟率以及 6 个月时的点患病率戒断率更高（65.1% vs 46.7%；OR，2.13；95% CI，1.32-3.43；P=0.002）。在联合治疗组中，恶心、睡眠障碍、皮肤反应、便秘和抑郁的发生率更高，但只有皮肤反应有统计学意义（14.4% vs 7.8%；P=0.03）；而伐尼克兰单药组出现更多的异常梦境和头痛。
在 12 周（治疗结束时）和 6 个月时，伐尼克兰联合 NRT 比单独使用伐尼克兰更能有效地实现烟草戒断。还需要进一步的研究来评估长期的疗效和安全性。
clinicaltrials.gov 标识符：NCT01444131。
