A SMART Approach to Treating Tobacco Use Disorder in Persons Living with HIV

治疗艾滋病毒感染者烟草使用障碍的明智方法

• 批准号: 10247005
• 负责人: Steven L Bernstein
• 金额: $ 66.31万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247005
• 关键词: Abstinence; Acquired Immunodeficiency Syndrome; Address; Adult; Agonist; Algorithms; Behavior Therapy; Behavioral; Biological Markers; CD4 Lymphocyte Count; Carbon Monoxide; Cardiovascular Diseases; Caring; Cause of Death; Chronic; Clinic; Clinical Pathways; Clinical Pharmacists; Clinical Trials; Clinical Trials Design; Conduct Clinical Trials; Data; Data Analyses; Enrollment; Evaluation; Exhalation; Future; General Population; Goals; HIV; Health; Health Services; Health system; Healthcare Systems; Incentives; Individual; Intervention; Leadership; Life Expectancy; Lung diseases; Malignant Neoplasms; Measures; Medical; Medication Management; Mental Depression; Meta-Analysis; Morbidity - disease rate; New York; Nicotine; Outcome; Pain; Participant; Patient Care; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacists; Prize; Process; Promoting Action on Research Implementation in Health Services framework; Publishing; Randomized; Reach, Effectiveness, Adoption, Implementation, and Maintenance; Regimen; Relapse; Reproducibility; Research; Research Design; Rewards; Role; Sample Size; Sampling; Sequential Multiple Assignment Randomized Trial; Site; Smoke; Smoker; Smoking; Specific qualifier value; Testing; Time; Tobacco; Tobacco Use Disorder; Tobacco use; Training; Treatment Protocols; United States Health Resources and Services Administration; United States National Institutes of Health; Viral; Viral Load result; addiction; antiretroviral therapy; arm; base; behavior change; behavioral pharmacology; cigarette smoke; cigarette smoking; clinically relevant; cohort; comparative effectiveness; contingency management; design; effectiveness implementation study; effectiveness study; evidence base; implementation science; improved; indexing; information gathering; innovation; mortality; mortality risk; multidisciplinary; neglect; nicotine replacement; non-smoking; novel; optimal treatments; primary outcome; randomized trial; receptor; responders and non-responders; response; smoking abstinence; smoking cessation; smoking intervention; smoking prevalence; tobacco cessation intervention; treatment response; treatment strategy; trial design; varenicline; years of life lost

ABSTRACT Smoking is the leading threat to health of patients living with HIV (PLWH). Unfortunately, the evidence-base for tobacco use disorder treatment in PLWH lags behind that of HIV itself. A 2016 Cochrane meta-analysis of data from 12 clinical trials involving 2,087 participants receiving both medications and behavioral support found modest evidence of improved abstinence in the short term (<6 months), but not long-term. A short-coming of these studies is that treatment algorithms did not include plans for non-response, or relapse to smoking. A newer clinical trial design, the Sequential Multiple Assignment Randomized Trial (SMART), includes a dynamic treatment strategy in which pre- specified decision rules guide the ongoing treatment of both responders and non-responders. This approach allows SMART designs to better mirror the management of chronic relapsing conditions, such as tobacco use disorder. We, therefore, propose a two-arm, two-stage randomized trial of 622 adult PLWH who smoke cigarettes and receive care in one of three health systems. At inception, participants will be randomized to either combination nicotine replacement therapy (NRT) (patch and gum or lozenge) or combination NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed by exhaled carbon monoxide [eCO]) in both arms will receive 12 more weeks of the same treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with varenicline (VAR) or varenicline+CM (VAR+CM). The intervention will be delivered by trained clinical pharmacists. The primary outcome will be eCO-confirmed abstinence at 24 weeks post-enrollment. The specific aims of the proposed study are to: (1) study the effectiveness of a dynamic treatment approach to reduce the prevalence of smoking in a cohort of PLWH, and to identify the optimal approach; (2), study the effectiveness of various dynamic regimens on CD4 count, HIV viral suppression, and VACS index (validated measure of morbidity and mortality risk); and (3) grounded in implementation science and using a Hybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation. The study team includes individuals with expertise in tobacco use disorder treatment, HIV and addiction in PLWH, clinical trials, CM, implementation science, and SMART designs. Study components are readily scalable and all interventions are richly evidence-based. This proposal offers innovation as the first use of the following in a smoking intervention targeting PLWH: (1) a SMART design with first-line tobacco treatment medications; (2) clinical pharmacists as key interventionists; (3) VACS Index 2.0 as an outcome among a general sample of PLWH who smoke; and (4) implementation-focused process evaluation of tobacco intervention including pharmacists and CM in HIV clinics. This study holds exceptional promise to transform tobacco use disorder treatment in HIV treatment settings nationally.

摘要 吸烟是对艾滋病毒感染者(PLWH)健康的主要威胁。不幸的是，证据基础 PLWH对烟草使用障碍的治疗落后于艾滋病毒本身。Cochrane 2016年对以下数据的元分析 涉及2,087名同时接受药物和行为支持的参与者的12项临床试验发现 短期(6个月)禁欲改善的证据，但不是长期的。这些研究的不足之处在于 治疗算法不包括无反应或重新吸烟的计划。更新的临床试验设计， 序贯多分配随机试验(SMART)包括一种动态治疗策略，其中预 具体的决定规则指导对应答者和非应答者的持续治疗。这种方法允许 智能设计，以更好地反映慢性复发情况的管理，如烟草使用障碍。我们, 因此，建议对622名吸烟和接受护理的成人PLWH进行双臂、两阶段随机试验 在三种医疗系统中的一种。一开始，参与者将随机服用两种尼古丁中的任何一种 替代疗法(NRT)(贴片、口香糖或含片)或联合NRT+应急处理(CM)。在12岁时 几周后，双臂中的应答者(由呼出的一氧化碳[ECO]确认的不吸烟参与者)将 再接受12周的相同治疗。无响应者(通过自我报告持续吸烟的参与者 和/或ECO)在NRT和NRT+CM组中都将被重新随机分配到12周的治疗中， Varenicline(VAR)或varenicline+CM(VAR+CM)。干预措施将由训练有素的临床药剂师提供。 主要结果将是在注册后24周内生态确认的禁欲。《公约》的具体目标 建议的研究是：(1)研究动态治疗方法的有效性，以降低患病率 在吸烟的PLWH队列中，找出最优的方法；(2)研究各种动态的有效性 治疗方案包括CD4计数、HIV病毒抑制和Vacs指数(发病率和死亡率风险的有效衡量标准)； 以及(3)以实施科学为基础，使用混合有效性-实施类型I设计，确定 提供我们的干预措施的障碍和促进者，为今后的执行提供信息。研究小组包括 在烟草使用障碍治疗、艾滋病和艾滋病成瘾治疗、临床试验、 实施科学和智能设计。研究组件易于扩展，并且所有干预措施都非常丰富 以证据为基础。这项提议提供了创新，作为吸烟干预靶向中第一次使用以下内容 PLWH：(1)一线烟草治疗药物的智能设计；(2)临床药剂师是关键 干预者；(3)Vacs指数2.0作为吸烟的PLWH普通样本的结果；和(4) 以实施为重点的烟草干预过程评估，包括药剂师和艾滋病毒诊所的CM。这 这项研究特别有希望改变全国艾滋病毒治疗环境中的烟草使用障碍治疗。