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.

抽象的 吸烟是艾滋病毒感染者 (PLWH) 健康的主要威胁。不幸的是，证据基础 艾滋病病毒感染者的烟草使用障碍治疗落后于艾滋病毒本身。 2016 年 Cochrane 数据分析 涉及 2,087 名接受药物和行为支持的参与者的 12 项临床试验发现效果不大 短期（<6 个月）内禁欲改善的证据，但长期效果不佳。这些研究的一个缺点是 治疗算法不包括无反应或复吸的计划。较新的临床试验设计， 序贯多重分配随机试验 (SMART)，包括动态治疗策略，其中预 明确的决策规则指导对应答者和非应答者的持续治疗。这种方法允许 SMART 设计旨在更好地反映慢性复发性疾病的管理，例如烟草使用障碍。我们， 因此，建议对 622 名吸烟并接受护理的成年感染者进行双组、两阶段随机试验 三个卫生系统之一。一开始，参与者将被随机分配到尼古丁组合 替代疗法 (NRT)（贴剂和口香糖或含片）或组合 NRT+应急管理 (CM)。 12 点 几周后，反应者（通过呼出一氧化碳 [eCO] 确认的非吸烟参与者）双臂将 再接受 12 周相同的治疗。无反应者（自我报告持续吸烟的参与者 NRT 和 NRT+CM 组中的（和/或 eCO）将被重新随机分配到 12 周的治疗，或者使用 伐尼克兰 (VAR) 或伐尼克兰+CM (VAR+CM)。干预措施将由经过培训的临床药剂师进行。 主要结果将是入组后 24 周经 eCO 确认的戒酒情况。该计划的具体目标 拟议的研究目的是：（1）研究动态治疗方法降低患病率的有效性 在一组感染者中吸烟，并确定最佳方法； (2)、研究各种动态的有效性 CD4 计数、HIV 病毒抑制和 VACS 指数（经过验证的发病率和死亡风险衡量标准）治疗方案； (3) 以实施科学为基础并使用混合有效性-实施类型 I 设计，确定 为未来的实施提供干预措施的障碍和促进因素。研究团队包括 在烟草使用障碍治疗、艾滋病毒感染者和艾滋病患者成瘾、临床试验、CM、 实施科学和智能设计。研究组成部分很容易扩展，所有干预措施都丰富 以证据为基础。该提案提供了创新，作为在吸烟干预目标中首次使用以下内容 PLWH：（1）采用一线烟草治疗药物的 SMART 设计； （二）临床药师为重点 干预主义者； (3) VACS 指数 2.0 作为吸烟感染者一般样本的结果；和（4） 以实施为重点的烟草干预过程评估，包括艾滋病毒诊所的药剂师和 CM。这 该研究有望改变全国艾滋病毒治疗机构中烟草使用障碍的治疗方法。