A clinical trial of adaptive treatment for early smoking cessation relapse

摘要 大多数吸烟者想要戒烟，大多数吸烟者每年都尝试戒烟。然而，大多数戒烟的尝试 吸烟失败FDA批准的药物治疗可以帮助，但无反应，无论是通过复发或通过 无法启动停止，仍然是最常见的结果。尽管治疗无反应的频率很高， 很少有试验研究了在这些情况下的最佳治疗途径--吸烟者是否应该尝试戒烟 再次使用相同的药物治疗，与包装指南一致，继续治疗12 还是应该预先预防早期失败并改变药物治疗？此外，对于吸烟者 对于那些多次尝试通过药物治疗戒烟但仍在吸烟的人， 有害的烟草产品，而不是试图用FDA批准的药物治疗反复戒烟？的 拟议的适应性治疗试验将测试1）在最初的适应性治疗后， 失败比重复尝试相同的药物治疗更能促进禁欲，以及2）是否 在多次药物治疗连续失败后改用电子烟更好地促进了 戒烟的成功率要比用同样疗程的药物治疗戒烟的三分之一高。每日吸烟 南卡罗来纳州和亚拉巴马愿意设定戒烟日期的受试者（N=544）将获得为期4周的 提供FDA批准的戒烟药物，并提供设定日期和戒烟的说明 完全吸烟。第一疗程药物将是尼古丁替代疗法 （透皮尼古丁贴片和口服尼古丁含片）或伐尼克兰，平衡。四周后 治疗，那些对初始治疗没有反应的人（即，无应答者）将以2：1的比例分配 适应性治疗（药物转换）或非适应性治疗（药物持续; 目标1）。在第二个4周治疗后，无应答者将以2：1的方式被分配至以下两组： 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 （药物持续;目标2），再次说明转换或完全退出。成果包括 经生化证实的7天戒烟、吸烟减少、依赖性指标、持续时间 在关键干预时间点测量：每个疗程后， 随访6个月。这一创新的R 01应用程序由两名经验丰富的研究人员领导， 戒烟、减少危害和远程临床试验。这个研究问题意义重大， 定位于为最常见问题的治疗决策提供强有力的数据驱动指导 即使是最好的吸烟治疗方法：失败。试验结果提供了一个重要的机会， 戒烟结果对于那些继续戒烟的人来说。

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.