An Effectiveness Trial of Maintenance Therapy for Nicotine Dependence

尼古丁依赖维持治疗的有效性试验

• 批准号: 8225360
• 负责人: Robert A Schnoll
• 金额: $ 60.16万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8225360
• 关键词: Abstinence; Acute; Address; Adoption; Adult; Adverse effects; Affect; Aftercare; Asthma; Behavioral; Chronic; Chronic Disease; Clinical Trials; Computer Simulation; Counseling; Data; Databases; Diabetes Mellitus; Dose; Effectiveness; Eligibility Determination; Europe; Evaluation; Event; Exclusion Criteria; Exhibits; Failure; Future; Gender; Goals; Guidelines; Health; Health Care Costs; Healthy People 2010; Heroin Dependence; Hypertension; Individual; Individual Differences; Life; Maintenance; Maintenance Therapy; Masks; Mediator of activation protein; Medical; Mental Depression; Metabolism; Methods; Modeling; Nature; Nicotine; Nicotine Dependence; Opiate Addiction; Outcome; Participant; Pattern; Placebo Control; Placebos; Prevalence; Publishing; Race; Randomized; Randomized Controlled Clinical Trials; Recommendation; Recovery; Regimen; Relapse; Research; Research Design; Rest; Risk; Safety; Serious Adverse Event; Smoker; Smoking; Therapeutic; Third-Party Payer; Tobacco Dependence; Tobacco Use Cessation; Tobacco use; Treatment outcome; United States Dept. of Health and Human Services; United States Public Health Service; Withdrawal; Withdrawal Symptom; active method; arm; base; community setting; cost effective; cost effectiveness; craving; design; economic cost; effectiveness trial; efficacy trial; evidence base; methadone maintenance; nicotine craving; nicotine patch; nicotine replacement; prevent; primary outcome; response; smoking cessation; standard care; treatment duration; treatment effect; trial comparing

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.

描述（由申请人提供）：尼古丁透皮贴剂是美国和欧洲最广泛使用的烟草依赖治疗形式。然而，贴片治疗后的戒断率在6个月时仅为~20%，在12个月时仅为~9%。越来越多的人认识到尼古丁依赖是一种慢性疾病，就像哮喘或糖尿病一样，需要维持治疗。虽然美国DHHS公共卫生服务（PHS）制定的现行指南建议尼古丁透皮治疗持续8周，但对这一建议的支持有限。在最近的一项随机安慰剂对照疗效试验中，比较了标准（8周）与扩展我们发现，在24周时，24周组的点患病率戒烟率为30%，而标准治疗组为20（p < .05）;然而，到第52周，即延长治疗组停止治疗后6个月，治疗组间的戒烟率相等。这是第一项临床试验，表明经皮尼古丁延长治疗的益处在很大程度上取决于积极治疗的持续性。然而，作为一项有效性试验，本研究是在严格的纳入/排除标准的高度对照条件下进行的，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，则必须在有效性试验中在“真实环境”下复制和扩展这些发现。此外，与支持使用美沙酮维持治疗阿片类药物依赖的临床试验一样，重复研究必须包括一个在整个试验期间（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剂戒烟维持治疗的益处。具体而言，660名吸烟者将接受简短的咨询，并将随机接受：标准（8周），延长（24周）或维持（52周）经皮尼古丁治疗。主要结局将是第52周时经生化验证的7天时点戒烟率。其他研究目的包括评估：1）研究组间的治疗副作用; 2）治疗组间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。总的来说，试验结果将为未来PHS对经皮尼古丁维持治疗的审查提供关键数据，用于后续治疗指南;第三方付款人评估维持经皮尼古丁作为覆盖的益处;以及个人吸烟者决定通过非处方药使用维持经皮尼古丁。反过来，这项研究可能有助于实现2010年健康人群的目标，即降低美国的烟草使用率。公共卫生相关性：透皮尼古丁贴片是美国和欧洲最广泛使用的烟草依赖治疗形式，但大多数吸烟者无法成功戒烟。对这种治疗没有反应可能在很大程度上是由于尼古丁贴片的使用仅为8周，这是推荐的治疗持续时间。我们在一项随机对照临床试验中发现，使用尼古丁贴片24周可以显着提高戒烟率。我们在这里提出了一个临床试验，复制和扩展这些结果，在现实世界中的社区设置，使用相同的研究设计在临床试验中使用，以证明美沙酮维持治疗阿片类药物依赖的有效性。具体而言，660名吸烟者将接受咨询和标准（8周），延长（24周）或维持（52周）尼古丁透皮贴剂治疗。主要结果是在第52周时经生化验证的戒烟。成本效益、安全性和作用机制（例如，促进失效后的恢复）。研究结果可能会改变我们如何用透皮尼古丁治疗尼古丁依赖。