Bohadana Abraham, Freier-Dror Yossi, Peles Vardit, Babai Polina, Izbicki Gabriel
Respiratory Research Unit, Pulmonary Institute, Shaare Zedek Medical Center, Affiliated with the Hadassah School of Medicine, Hebrew University of Jerusalem, 12 Baiyt Street, Jerusalem 91031, Israel.
Mashav Applied Research, 5 Chail Nashim Street, Jerusalem 9332005, Israel.
EClinicalMedicine. 2020 Feb 3;19:100228. doi: 10.1016/j.eclinm.2019.11.021. eCollection 2020 Feb.
Initiating varenicline use 4 weeks before the target quit date (TQD) reduces smoking in the run-in phase and increases end-treatment cessation rates; however, the lack of a smoke intake plateau suggests longer preloading periods are required. This study assessed whether varenicline preloading for 6 weeks reduced pre-quit smoke intake and enhanced 6-month abstinence outcomes compared with the standard 1-week preloading.
In this randomised single-centre controlled trial, (ClinicalTrials.gov identifier: NCT02634281), conducted between February 2016 and July 2018 in Israel, daily smokers ( = 242) aged ≥ 18 years were randomly assigned (1:1) to receive varenicline preloading for 6 weeks ( = 121) or a placebo for 5 weeks followed by varenicline for 1 week ( = 121) before the TQD. Participants and researchers were masked to both group assignment and treatment allocation. Both groups received standard 12-week post-TQD varenicline treatment. The primary outcome was the 24-week biochemically verified continuous abstinence rate (CAR) from weeks 6 (TQD)-30. Secondary outcomes included the 23-week CAR from 1-week post-TQD (week 7) to week 30, and the 7-day point-prevalence (PP) abstinence at week 30. Other measures included pre- and post-quit rewards, smoking urges, nausea, aversion, and markers of cigarette consumption.
By intention-to-treat, the 24-week CAR, weeks 6-30 with extended preloading was significantly higher than with standard preloading (23·1% vs. 4·1%; risk reduction [RR]: -0·19 [95% confidence interval [CI]:-0·10-0·24]; < 0·001). Extended preloading also showed better secondary outcomes. Extended preloading significantly decreased pre-quit rewards, urges, and smoke intake, including unsolicited smoking abstinence. Post-quit urges remained remarkably lower with extended preloading. Participants receiving extended preloading reported more nausea at week 4 (39.6% vs 11.5%) and abnormal dreams at week 6 (7.7% vs. 0%). Participants receiving standard preloading reported more constipation at week 7 (7.6% vs. 0%) and dizziness at weeks 7 (12.1% vs. 2.5%) and 12 (10.7% vs 1.4%).
Extended preloading reduced smoking, enhanced cessation rates at 3 and 6 months, and decreased pre- and post-quit rewards and smoking drive in a pattern compatible with a reinforcement-reduction mechanism. These data substantiate extending the standard pre-treatment period, and suggest that targeting pre-quit smoking sensations should be a treatment priority, although confirmatory evidence is needed from larger clinical trials.
This study was funded by a 2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc. (#WI182915).
在目标戒烟日期（TQD）前4周开始使用伐尼克兰可减少导入期的吸烟量并提高治疗结束时的戒烟率；然而，缺乏吸烟量平稳期表明需要更长的预加载期。本研究评估了与标准的1周预加载相比，6周的伐尼克兰预加载是否能减少戒烟前的吸烟量并提高6个月的戒烟成功率。
在2016年2月至2018年7月于以色列进行的这项随机单中心对照试验（ClinicalTrials.gov标识符：NCT02634281）中，年龄≥18岁的每日吸烟者（n = 242）被随机分配（1:1）接受6周的伐尼克兰预加载（n = 121）或5周的安慰剂，然后在TQD前1周接受伐尼克兰（n = 121）。参与者和研究人员对分组和治疗分配均不知情。两组在TQD后均接受标准的12周伐尼克兰治疗。主要结局是从第6周（TQD）至第30周经生化验证的24周持续戒烟率（CAR）。次要结局包括从TQD后1周（第7周）至第30周的23周CAR，以及第30周的7天点患病率（PP）戒烟率。其他指标包括戒烟前后的奖励、吸烟冲动、恶心、厌恶以及香烟消费指标。
按意向性分析，延长预加载期（第6 - 30周）的24周CAR显著高于标准预加载期（23.1%对4.1%；风险降低[RR]：-0.19[95%置信区间[CI]：-0.10 - 0.24]；P < 0.001）。延长预加载期在次要结局方面也表现更好。延长预加载期显著降低了戒烟前的奖励、冲动和吸烟量，包括非主动戒烟。延长预加载期后戒烟后的冲动仍显著更低。接受延长预加载期的参与者在第4周报告更多恶心（39.6%对11.5%），在第6周报告更多异常梦境（7.7%对0%）。接受标准预加载期的参与者在第7周报告更多便秘（7.6%对0%），在第7周（12.1%对2.5%）和第12周（10.7%对1.4%）报告更多头晕。
延长预加载期可减少吸烟量，提高3个月和6个月时的戒烟率，并以与强化减少机制相符的模式降低戒烟前后的奖励和吸烟动力。这些数据证实了延长标准预处理期的合理性，并表明针对戒烟前的吸烟感觉应作为治疗重点，尽管需要更大规模临床试验的验证性证据。
本研究由辉瑞公司支持的2013年全球尼古丁依赖研究奖（GRAND）资助（#WI182915）。
