[DATABASE] Comparing the Effectiveness, Tolerability, and Acceptability of Heated Tobacco Products and Refillable Electronic Cigarettes for Cigarette Substitution (CEASEFIRE): Randomized Controlled Trial

Background: People who smoke and who face challenges trying to quit or wish to continue to smoke may benefit by switching from traditional cigarettes to noncombustible nicotine delivery alternatives, such as heated tobacco products (HTPs) and electronic cigarettes (ECs). HTPs and ECs are being increasingly used to quit smoking, but there are limited data about their effectiveness.

Objective: We conducted the first randomized controlled trial comparing quit rates between HTPs and ECs among people who smoke and do not intend to quit.

Methods: We conducted a 12-week randomized noninferiority switching trial to compare effectiveness, tolerability, and product satisfaction between HTPs (IQOS 2.4 Plus) and refillable ECs (JustFog Q16) among people who do not intend to quit. The cessation intervention included motivational counseling. The primary endpoint of the study was the carbon monoxide-confirmed continuous abstinence rate from week 4 to week 12 (CAR weeks 4-12). The secondary endpoints included the continuous self-reported ≥50% reduction in cigarette consumption rate (continuous reduction rate) from week 4 to week 12 (CRR weeks 4-12) and 7-day point prevalence of smoking abstinence.

Results: A total of 211 participants completed the study. High quit rates (CAR weeks 4-12) of 39.1% (43/110) and 30.8% (33/107) were observed for IQOS-HTP and JustFog-EC, respectively. The between-group difference for the CAR weeks 4-12 was not significant (P=.20). The CRR weeks 4-12 values for IQOS-HTP and JustFog-EC were 46.4% (51/110) and 39.3% (42/107), respectively, and the between-group difference was not significant (P=.24). At week 12, the 7-day point prevalence of smoking abstinence values for IQOS-HTP and JustFog-EC were 54.5% (60/110) and 41.1% (44/107), respectively. The most frequent adverse events were cough and reduced physical fitness. Both study products elicited a moderately pleasant user experience, and the between-group difference was not significant. A clinically relevant improvement in exercise tolerance was observed after switching to the combustion-free products under investigation. Risk perception for conventional cigarettes was consistently higher than that for the combustion-free study products under investigation.

Conclusions: Switching to HTPs elicited a marked reduction in cigarette consumption among people who smoke and do not intend to quit, which was comparable to refillable ECs. User experience and risk perception were similar between the HTPs and ECs under investigation. HTPs may be a useful addition to the arsenal of reduced-risk alternatives for tobacco cigarettes and may contribute to smoking cessation. However, longer follow-up studies are required to confirm significant and prolonged abstinence from smoking and to determine whether our results can be generalized outside smoking cessation services offering high levels of support.

背景：吸烟且在戒烟过程中存在困难，或仍希望继续吸烟的人群，可通过将传统卷烟替换为非可燃尼古丁递送替代产品获益，例如加热烟草制品（heated tobacco products, HTPs）与电子烟（electronic cigarettes, ECs）。目前HTPs与ECs正越来越多地被用于戒烟，但关于其有效性的相关数据仍较为有限。
研究目的：本研究开展了首项随机对照试验，旨在针对无意戒烟的吸烟人群，对比HTPs与ECs的戒烟成功率。
研究方法：本研究开展了一项为期12周的随机非劣效性转换试验，针对无意戒烟的吸烟人群，对比HTPs（IQOS 2.4 Plus）与可注油式电子烟（JustFog Q16）的有效性、耐受性及产品满意度。本次戒烟干预包含动机性咨询。本研究的主要终点为第4周至第12周的经一氧化碳确认的持续戒断率（CAR 4-12周）。次要终点包括第4周至第12周自我报告的卷烟消费量持续减少≥50%的比例（持续减少率，CRR 4-12周），以及7天时点吸烟戒断率。
研究结果：共计211名受试者完成本研究。IQOS-HTP组与JustFog-EC组的CAR 4-12周戒断率分别为39.1%（43/110）与30.8%（33/107），组间差异无统计学意义（P=0.20）。IQOS-HTP组与JustFog-EC组的CRR 4-12周分别为46.4%（51/110）与39.3%（42/107），组间差异无统计学意义（P=0.24）。在第12周时，IQOS-HTP组与JustFog-EC组的7天时点吸烟戒断率分别为54.5%（60/110）与41.1%（44/107）。最常见的不良事件为咳嗽与体能下降。两款研究产品均带来了中等程度的良好使用体验，组间差异无统计学意义。转换至本次研究的无燃烧产品后，受试者的运动耐量出现了具有临床意义的改善。受试者对传统卷烟的风险认知始终高于本次研究中的无燃烧产品。
研究结论：对于无意戒烟的吸烟人群，转换使用HTPs可显著降低其卷烟消费量，该效果与可注油式电子烟相当。本次研究中HTPs与ECs的使用体验及风险认知水平相似。HTPs可作为烟草卷烟减害替代方案的有效补充，有助于实现戒烟。不过，仍需开展更长随访周期的研究，以确认长期、显著的吸烟戒断效果，并明确本研究结果能否推广至未提供高水平支持的戒烟服务场景之外。