Achieving smoking cessation milestones in opioid treatment patients: a randomized 2 x 2 factorial trial of directly observed and long-term varenicline

摘要 烟草使用和烟草相关疾病在阿片类药物使用障碍患者中非常普遍 （OUD）。不幸的是，传统的循证戒烟干预措施的戒烟率很低， 在这个群体中戒烟。大多数评估戒烟治疗干预措施的试验 OUD患者依赖于短期干预措施，而这些干预措施并不能解决OUD患者面临的独特挑战。 这些吸烟者所面临的问题，特别是建立初始戒烟，坚持循证戒烟， 治疗，并保持禁欲一旦积极治疗停止。长期戒烟 药物治疗方法在促进戒烟和减少复发方面显示出希望， 没有OUD的人，然而，扩展药物治疗方法对OUD吸烟者的适用性 可能受到戒烟药物依从性差的限制。虽然坚持戒烟 药物治疗与戒烟成功密切相关，对于患有以下疾病的人来说，坚持治疗尤其具有挑战性 OUD。基于阿片类药物治疗计划的直接观察治疗（DOT）干预改善了临床 我们的试验数据表明，DOT伐尼克兰与吸烟增加有关， 戒烟药物依从性，并可能增加戒烟率。因此，我们建议采用2x2 析因、随机、双盲、安慰剂对照试验，有效检验两种干预措施：直接 观察药物治疗和长期伐尼克兰治疗。我们的分析策略将评估 戒烟的里程碑-实现初步戒烟，防止戒烟和防止复吸- 长期戒烟所必需的，并评估理论指导的心理和社会因素， 药物遗传学因素影响这些停止过程。我们将招募450名OUD吸烟者， 社区为基础的，门诊阿片类药物治疗计划，并测试以下具体目标：（1）测试 直接观察伐尼克兰治疗与自我给药伐尼克兰治疗对吸烟的疗效比较 停止里程碑，（2）测试长期伐尼克兰与短期伐尼克兰相比对 戒烟里程碑，以及（3）通过检查戒烟的机制， 理论引导的心理和社会因素以及药物遗传学因素对戒烟的影响 里程碑这一建议具有创新性，解决了促进和维护 吸烟者戒烟与OUD。

ABSTRACT Tobacco use and tobacco-related disease are highly prevalent among persons with opioid use disorders (OUD). Unfortunately, traditional evidence-based smoking cessation interventions have yielded low rates of tobacco abstinence in this group. The majority of trials evaluating smoking cessation treatment interventions among persons with OUD have relied on short-term interventions that do not account for the unique challenges faced by these smokers, specifically, establishing initial abstinence, adhering to evidence-based cessation treatments, and maintaining abstinence once active treatments cease. Long-term smoking cessation medication treatment approaches have shown promise in promoting cessation and decreasing relapse among individuals without OUD, however the applicability of extended medication approaches to smokers with OUD may be limited by poor adherence to smoking cessation medications. Though adherence to cessation medication is strongly associated with cessation success, adherence is especially challenging for persons with OUD. Opioid treatment program-based directly observed therapy (DOT) interventions improve clinical outcomes in HIV and TB, and our pilot data suggest that DOT varenicline is associated with increased smoking cessation medication adherence and may increase smoking cessation rates. We therefore propose a 2 x 2 factorial, randomized, double-blind, placebo-controlled trial to efficiently test two interventions: directly observed medication therapy, and long-term therapy with varenicline. Our analytic strategy will evaluate the milestones in smoking cessation—achieving initial abstinence, preventing lapse and preventing relapse-- necessary for long-term cessation, and evaluate theoretically-guided psychological and social factors and pharmacogenetic factors that influence these cessation processes. We will recruit 450 smokers with OUD from community-based, outpatient opioid treatment programs and test the following specific aims: (1) to test the efficacy of directly observed varenicline therapy compared to self-administered varenicline therapy on smoking cessation milestones, (2) to test the efficacy of long-term varenicline compared to short-term varenicline on smoking cessation milestones, and (3) to understand the mechanism of smoking cessation by examining the impact of theory-guided psychological and social factors and of pharmacogenetic factors on cessation milestones. This proposal is innovative, and addresses the challenges of both promoting and maintaining tobacco abstinence among smokers with OUD.