An Effectiveness Trial of Maintenance Therapy for Nicotine Dependence

描述(申请人提供)：尼古丁透皮贴片是美国和欧洲使用最广泛的烟草依赖治疗形式。然而，贴片治疗后的禁酒率在6个月时仅为~20%，在12个月时为~9%。越来越多的人认识到，尼古丁依赖是一种慢性病，就像哮喘或糖尿病一样，需要维持治疗。虽然美国卫生部公共卫生服务(PHS)目前制定的指南建议尼古丁透皮治疗持续8周，但对这一建议的支持是有限的。在最近的一项随机安慰剂对照疗效试验中，我们对尼古丁贴片的标准(8周)和延长(24周)治疗进行了比较，我们发现，在24周时，24周组的点流行戒断率为30%，标准治疗组为20%(p&lt；0.05)；然而，到52周，即延长治疗组停止治疗6个月后，两组治疗组的戒烟率相同。这是第一次临床试验表明，延长尼古丁透皮治疗的益处在很大程度上取决于继续积极治疗。然而，作为一项有效性试验，这项研究是在高度受控的条件下进行的，具有严格的纳入/排除标准，以提高内部效度。如果要正式修订尼古丁贴片治疗持续时间的建议，以鼓励维持治疗，这些发现必须在有效性试验中的“真实世界环境”下重复和推广。此外，正如在支持使用美沙酮维持治疗阿片类药物依赖的临床试验中所做的那样，重复研究必须包括在整个试验期间(52周)接受维持治疗的治疗组。因此，我们建议进行一项随机有效性试验，以评估尼古丁透皮贴片维持治疗戒烟的益处。具体来说，660名吸烟者将接受简短的咨询，并将被随机分为：标准(8周)、延长(24周)或维持(52周)尼古丁透皮治疗。主要结果将是在第52周进行生化验证的7天点戒酒。其他研究目标包括评估：1)跨研究分支的治疗副作用；2)跨治疗分支的复发和恢复的纵向模式；3)治疗效果的中介者和调节者；以及4)成本效益。总体而言，试验结果将为未来PHS对尼古丁透皮维持疗法的审查提供关键数据，用于后续治疗指南；为第三方支付者评估维持透皮尼古丁作为承保福利；以及为个人吸烟者通过非处方药使用维持透皮尼古丁的决定提供关键数据。反过来，这项研究可能有助于实现健康人2010年降低美国烟草使用率的目标。公共卫生相关性：尼古丁透皮贴片是美国和欧洲使用最广泛的烟草依赖治疗形式，但大多数吸烟者无法成功戒烟。这种治疗无效在很大程度上可能是因为只使用了8周的尼古丁贴片，这是推荐的治疗持续时间。我们在一项对照随机临床试验中发现，使用尼古丁贴片24周可以显著提高戒烟率。在这里，我们建议进行一项临床试验，将这些结果复制并扩展到现实世界的社区环境中，使用临床试验中使用的相同研究设计来证明美沙酮维持疗法对阿片类药物依赖的有效性。具体来说，660名吸烟者将接受咨询和标准(8周)、延长(24周)或维持(52周)尼古丁贴片治疗。主要结果是在52周时生物化学证实戒烟。还将评估尼古丁透皮维持疗法的成本效益、安全性和作用机制(例如，在失效后促进康复)。研究结果可能会改变我们用尼古丁透皮治疗尼古丁依赖的方式。

DESCRIPTION (provided by applicant): The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe. Yet, abstinence rates following patch treatment are only ~20% at 6-months and ~9% at 12-months. There is a growing recognition that nicotine dependence is a chronic disease, like asthma or diabetes, which requires maintenance therapy. While current guidelines established by the US DHHS's Public Health Service (PHS) recommend 8-week duration for transdermal nicotine therapy, support for this recommendation is limited. In a recent randomized placebo-controlled efficacy trial comparing standard (8-week) vs. extended (24- weeks) treatment with nicotine patches, we found that, at 24 weeks, point-prevalence abstinence rates were 30% in the 24-week arm vs. 20% in the standard therapy arm (p < .05); however, by week 52, 6 months after treatment was discontinued for the extended treatment arm, the quit rates were equivalent across the treatment arms. This was the first clinical trial to suggest that the benefits of extended treatment with transdermal nicotine are largely dependent on the continuation of active treatment. However, as an efficacy trial, this study was conducted under highly-controlled conditions with strict inclusion/exclusion criteria to enhance internal validity. If recommendations for the duration of nicotine patch therapy are to be formally revised to encourage maintenance therapy, these findings must be replicated and extended under "real-world circumstances" in an effectiveness trial. In addition, as done in clinical trials to support the use of methadone maintenance for opiate dependence, a replication study must include a treatment arm that receives maintenance therapy throughout the duration of the trial (52 weeks). Thus, we propose to conduct a randomized effectiveness trial to evaluate the benefits of maintenance therapy with transdermal nicotine patches for smoking cessation. Specifically, 660 smokers will receive brief counseling and will be randomized to: standard (8-weeks), extended (24-weeks), or maintenance (52 weeks) transdermal nicotine therapy. The primary outcome will be bio-chemically verified 7-day point prevalence abstinence at week 52. Additional study aims include assessing: 1) treatment side effects across study arms; 2) longitudinal patterns of relapse and recovery across treatment arms; 3) mediators and moderators of treatment effects; and 4) cost-effectiveness. Overall, the trial findings will provide critical data for future PHS reviews of maintenance therapy with transdermal nicotine for subsequent treatment guidelines; for third-party payer assessments of maintenance transdermal nicotine as a covered benefit; and for individual smokers' decisions to use maintenance transdermal nicotine through over-the-counter access. In turn, this study may help to attain the Healthy People 2010 goals of reducing the US rate of tobacco use. PUBLIC HEALTH RELEVANCE: The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe, but most smokers are unable to successfully quit with this form of treatment. Failure to respond to this treatment may, to a large extent, be due to the use of nicotine patches for only 8 weeks, the recommended treatment duration. We have found in a controlled randomized clinical trial that using the nicotine patch for 24 weeks can increase quit rates significantly. We propose here a clinical trial to replicate and extend these results to a community setting in the real-world, using the same research design utilized in clinical trials to demonstrate the effectiveness of methadone maintenance therapy for opiate dependence. Specifically, 660 smokers will receive counseling and standard (8-weeks), extended (24-weeks), or maintenance (52 weeks) therapy with transdermal nicotine patches. The main outcome is bio-chemically verified smoking cessation at week 52. The cost-effectiveness, safety, and mechanism of effect (e.g., promotion of recovery following a lapse) for maintenance therapy with transdermal nicotine will also be assessed. The study results may change how we treat nicotine dependence with transdermal nicotine.