Metabolism Informed Smoking Treatment in Medicaid and Medicare Patients: The MIST RCT

医疗补助和医疗保险患者的代谢知情吸烟治疗：MIST 随机对照试验

• 批准号: 10377378
• 负责人: Hilary A. Tindle
• 金额: $ 84.28万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-08 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10377378
• 关键词: Abstinence; Academic Medical Centers; Adult; Aftercare; American; Biochemical; Biological Markers; Cessation of life; Clinical Treatment; Clinical Trials; Confidence Intervals; Consult; Cotinine; Counseling; Cytochrome P450; Data; Databases; Disease; Drug Prescriptions; Enrollment; Enzymes; FDA approved; Health system; Healthcare; Hospitalization; Hospitals; Information Systems; Infrastructure; Inpatients; Liver; Malignant Neoplasms; Medicaid; Medical; Medicare; Metabolism; Nicotine; Nicotine Dependence; Odds Ratio; Outcome; Outcome Study; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacogenomics; Pharmacotherapy; Pharmacy facility; Positioning Attribute; Prevalence; Provider; Publishing; Randomized; Records; Research; Research Personnel; Risk; Salivary; Smoke; Smoker; Smoking; Smoking Status; South American; Speed; Surveys; Telephone; Tennessee; Testing; Time; Tobacco; Tobacco use; Validation; Visit; Work; adherence rate; arm; base; beneficiary; cigarette smoking; clinical care; clinical implementation; clinical practice; design; health care service utilization; high risk; hydroxycotinine; improved; medication compliance; member; mortality; nicotine patch; personalized approach; pharmacy benefit; precision medicine; side effect; smoking abstinence; smoking cessation; smoking-related disease; success; treatment as usual; treatment response; treatment services; varenicline

Project Summary The American Southeast has some of the highest rates of cigarette smoking and smoking-attributable cancer mortality in the nation. Medicaid and Medicare (CMS) beneficiaries who smoke are at high risk of smoking- related disease, yet each year fewer than one in five CMS-enrolled smokers (and fewer than one in ten Tennessee Medicaid smokers) with pharmacy benefits receive smoking cessation medication. Furthermore, when smoking cessation medication is provided, it is not biologically tailored for maximum efficacy. The ratio of 3-hydroxycotinine to cotinine, known as the nicotine metabolite ratio (NMR), reflects CYP2A6 activity and the rate of nicotine metabolism. Among “normal” metabolizers as assessed by NMR, varenicline produces quit rates roughly double those of nicotine patch at 6 months (23% vs. 13%, p<0.05), while among “slow” metabolizers, quit rates do not differ by drug. The number needed to treat to help one normal metabolizer quit smoking is only 4.9 for varenicline vs. 26 for nicotine patch, establishing the scientific premise to pair normal metabolizers with varenicline and slow metabolizers with nicotine. We propose to test Metabolism-Informed Smoking Treatment (MIST), a precision approach that biologically tailors medication to nicotine metabolism, for CMS beneficiaries in the Mid-South who smoke. We hypothesize that MIST will be superior to usual care (UC), i.e., selection of medication uninformed by NMR, for smoking cessation. We randomized 81 adult daily smokers at Vanderbilt University Medical Center (VUMC) to MIST vs control. MIST increased NMR-medication match rates more than 3-fold: unadjusted odds ratio 3.67 (95% confidence interval 1.33-11.00; p-value=0.02), and was highly acceptable to patients. To assess the efficacy of MIST relative to UC for abstinence and its use by patients and providers in clinical practice, the MIST RCT will enroll 1,000 CMS-enrolled adult daily smokers who are hospitalized and counseled by the inpatient VUMC Tobacco Treatment Service. Specific AIMS are to compare the effects of MIST vs. UC on: (1) Abstinence at 6 months (1a, 1° study outcome), defined by biochemically-verified 7-day point prevalence abstinence, and 12 months (1b, 2° outcome); (2) Clinical implementation, defined by patient self-reported medication adherence (2a, 2° outcome), PCP prescription of medication for patients smoking after hospital discharge (2b, 2° outcome), and whether the prescription is NMR-matched (2c, 2° outcome); and (3) Health care utilization and mortality (exploratory) as tracked by existing databases including the statewide Tennessee Hospital Discharge Data System and CMS data. All participants will receive counseling and medication for tobacco use. Investigators have broad, complementary expertise in smoking cessation clinical trials, precision medicine, smoking pharmacogenomics, and use of large databases, and leverage extensive health system infrastructure. IMPACT: This is the first large RCT to incorporate nicotine metabolism into clinical care, and could fundamentally shift smoking treatment away from a generic approach and into the era of precision medicine.

项目摘要 美国东南部的吸烟和吸烟癌症的速度最高 全国死亡率。吸烟的医疗补助和医疗保险（CMS）受益人有吸烟的高风险 - 相关疾病，但每年不到五分之一的CMS吸烟者（少于十分之一） 田纳西州医疗补助吸烟者）有药房福利接受戒烟药物。此外， 当提供戒烟药物时，它不会在生物学上量身定制，以最大程度地效率。比率 3-羟基霉素与可替氨酸，称为尼古丁代谢物比（NMR），反映了CYP2A6活性和 尼古丁代谢的速率。在NMR评估的“正常”代谢器中，Varenicline产生戒烟 6个月时尼古丁斑块的比率约占尼古丁斑块的比例（23％比13％，p <0.05），而在“慢”中 代谢物，戒烟率与药物没有差异。治疗所需的数量以帮助一个普通的代谢器退出 Varenicline与尼古丁补丁的吸烟仅为4.9 具有Varenicline的代谢剂和尼古丁的慢速代谢剂。我们建议测试新陈代谢的信息 吸烟治疗（雾），一种精确的方法，可以生物学量身定制尼古丁的药物 代谢，对于中南吸烟的CMS受益人。我们假设雾将 优于通常的护理（UC），即NMR不知情的药物选择，以戒烟。我们 范德比尔特大学医学中心（VUMC）随机分配了81名成人每日吸烟者，以进行薄雾与控制。薄雾 NMR介绍率的增加超过3倍：未调整的优势比3.67（95％置信区间 1.33-11.00; p值= 0.02），患者高度可接受。评估雾的效率相对于 UC禁欲及其在临床实践中的患者和提供者的使用，MIST RCT将注册1000 CMS注册的成人每日吸烟者被住院烟草烟草住院和创造 治疗服务。具体目的是比较薄雾与UC的影响：（1）6岁时禁欲 月份（1a，1°研究结果），由生化验证的7天戒酒率定义，12 月份（1b，2°结果）； （2）由患者自我报告的药物依从性定义的临床实施 （2a，2°结果），住院后吸烟患者的PCP处方（2B，2°） 结果），以及处方是否为NMR匹配（2C，2°结果）； （3）医疗保健利用和 死亡率（探索性）如现有数据库所追踪的，包括田纳西州全州医院 放电数据系统和CMS数据。所有参与者都将获得有关烟草使用的咨询和药物。 研究人员在戒烟临床试验，精密医学方面拥有广泛的全面专业知识， 吸烟药物基因组学以及大型数据库的使用，并利用广泛的卫生系统基础设施。 影响：这是将尼古丁代谢纳入临床护理中的第一个大型RCT，并且可以 从根本上将吸烟治疗从通用方法转移到精密医学时代。