A clinical trial of adaptive treatment for early smoking cessation relapse

摘要 大多数吸烟者想要戒烟，而且大多数吸烟者每年都试图戒烟。然而，大多数戒烟的尝试 吸烟失败了。FDA批准的药物疗法可以帮助治疗，但没有反应，无论是通过复发还是通过 无法主动戒烟，仍然是最常见的结果。尽管治疗无反应的频率很高， 在这些情况下，很少有试验研究治疗的最佳途径--吸烟者是否应该尝试戒烟 再次使用相同的药物治疗，符合一揽子指南，继续治疗12个月 几周，还是应该预防早期的失败，并改变药物治疗？此外，对于吸烟者来说 已经多次尝试用药物治疗戒烟但仍在吸烟的人，是否最好改用较少的药物治疗 而不是尝试用FDA批准的药物疗法反复戒烟？这个 拟议的适应性治疗试验将测试1)在最初的 失败比反复尝试相同的药物疗法更能促进戒酒，以及2) 在多种药物疗法连续失败后改用电子烟更好地促进 戒烟比第三次尝试戒烟用同样的药物治疗要好。每日吸烟者 在南卡罗来纳州和阿拉巴马州，愿意设定戒烟日期(N=544)的人将获得为期4周的 提供FDA批准的戒烟药物，并提供确定日期和戒烟的说明 完全在抽烟。第一疗程的药物治疗将是尼古丁替代疗法的组合 (尼古丁透皮贴片和口服尼古丁含片)或伐伦克林，平衡。在经历了四周的 治疗，那些对初步治疗没有反应的人(即无反应者)将以2：1的比例分配 流行到适应性治疗(用药切换)或非适应性治疗(继续用药； 目标1)。在第二个四周的治疗后，无反应者将以2：1的方式被分配到任何一种伤害 减少方法(改用危害较小的烟草产品；电子烟)或非适应性治疗 (继续服药；目标2)，再次说明是否完全停止服药。结果包括 生物化学.确认的7天戒烟，减少吸烟，依赖的测量，持续时间 禁欲和双重用途，每个都在关键的干预时间点进行测量：在每个疗程之后， 随访6个月。这一创新的R01应用程序由两名具有专业知识的经验丰富的调查人员领导 在戒烟、减少危害和远程临床试验中。这一研究问题意义重大， 旨在为最常见问题的治疗决策提供强有力的、数据驱动的指导 即使是最好的吸烟疗法也要面对：失败。试验结果提供了一个重要的优化机会 继续在戒烟过程中挣扎的吸烟者的戒烟结果。

Abstract Most smokers want to quit smoking, and most smokers try to quit smoking each year. Yet, most attempts to quit smoking fail. FDA-approved pharmacotherapies can help, but non-response, either through relapse or through inability to initiate cessation, is still the most common outcome. Despite the frequency of treatment non-response, few trials have investigated the best path forward for treatment in these instances—should smokers try to quit again with the same pharmacotherapy, consistent with package guidelines to continue with treatment for 12 weeks, or should early failure be preempted and met with a change in pharmacotherapy? Further, for smokers who have tried to quit with pharmacotherapy multiple times and are still smoking, is it better to switch to a less harmful tobacco product rather than trying to quit repeatedly with FDA-approved pharmacotherapy? The proposed adaptive treatment trial will test whether 1) switching between pharmacotherapies following an initial failure better promotes abstinence than a repeated attempt with the same pharmacotherapy, and 2) whether switching to e-cigarettes following successive failures with multiple pharmacotherapies better promotes abstinence from cigarettes than a third attempt to quit with the same course of pharmacotherapy. Daily smokers across South Carolina and Alabama who are willing to set a quit date (N=544) will be provided with a 4-week supply of FDA approved smoking-cessation medication and provided with instructions to set a date and to quit smoking completely. First-course medication will be either combination nicotine replacement therapy (transdermal nicotine patch and oral nicotine lozenge) or varenicline, counterbalanced. After four weeks of treatment, those who have not responded to initial treatment (i.e., non-responders) will be assigned in a 2:1 fashion to either Adaptive Treatment (medication switch) or Non-Adaptive Treatment (medication continuance; Aim 1). After a second four weeks of treatment, non-responders will be assigned in a 2:1 fashion to either a Harm Reduction Approach (to switch to a less harmful tobacco product; e-cigarettes) or Non-Adaptive Treatment (medication continuance; Aim 2), again with instructions to switch or quit completely. Outcomes include biochemically-confirmed 7-day abstinence from smoking, smoking reduction, measures of dependence, duration of abstinence, and dual use, each measured at key intervention timepoints: after each course of treatment, with follow-up through six months. This innovative R01 application is led by two seasoned investigators with expertise in smoking cessation, harm reduction, and remote clinical trials. The research question is highly significant and is positioned to provide strong, data-driven guidance on treatment decision making for the most common problem facing even the best treatments for smoking: failure. Trial results provide a significant opportunity to optimize cessation outcomes for smokers who continue to struggle in quitting.