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: 9910370
• 负责人: Hilary A. Tindle
• 金额: $ 69.35万
• 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/9910370
• 关键词: Abstinence; Academic Medical Centers; Adult; Aftercare; American; Biochemical; Biological; Biological Markers; Cessation of life; Clinical Treatment; Clinical Trials; Confidence Intervals; Consult; Cotinine; Counseling; Cytochrome P450; Data; Databases; Disease; Enrollment; Enzymes; Estrogen receptor positive; 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; 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; 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 美国东南部的吸烟率和吸烟可归因于癌症的比率是最高的 全国的死亡率。吸烟的医疗补助和医疗保险(CMS)受益人吸烟的风险很高- 相关疾病，但每年参加CMS的吸烟者不到五分之一(不到十分之一 田纳西州医疗补助吸烟者)享受药房福利，接受戒烟药物治疗。此外， 当提供戒烟药物时，它并不是为达到最大疗效而量身定做的。的比例 3-羟基可替宁与可替宁的比值，称为尼古丁代谢物比率(核磁共振)，反映了CYP2A6的活性和 尼古丁代谢率。在核磁共振评估的“正常”代谢物中，varenicline可产生戒断 6个月后，尼古丁贴片的使用率大约是尼古丁贴片的两倍(23%对13%，p&lt；0.05)，而在“缓慢”之间。 代谢物，戒毒率因药物而异。帮助一名正常代谢者戒烟所需治疗的人数 使用varenicline的吸烟率仅为4.9，而使用尼古丁贴片的吸烟率为26，这为配对正常建立了科学前提 使用varenicline的代谢物和使用尼古丁的慢代谢物。我们建议测试新陈代谢-知情 吸烟治疗(MIST)，一种精确的方法，通过生物学方法为尼古丁量身定做药物 新陈代谢，对于中南部吸烟的CMS受益者。我们假设薄雾将会是 优于常规护理(UC)，即选择未经核磁共振通知的戒烟药物。我们 范德比尔特大学医学中心(VUMC)的81名成年每日吸烟者随机分为雾化组和对照组。薄雾 核磁共振-药物匹配率提高3倍以上：未调整的优势比3.67(95%可信区间 1.33~11.00；p值=0.02)，患者可接受程度较高。评估雾化喷雾的有效性 UC为禁欲及其患者和提供者在临床实践中的使用，MIST随机对照试验将招收1,000人 CMS登记的成人每日吸烟者，由住院的VUMC烟草公司住院和咨询 治疗服务。具体目的是比较雾化和UC在以下方面的效果：(1)在6岁时戒烟 月份(1a，1°研究结果)，由生化验证的7天点戒酒定义，以及12个月 月(1b，2°结果)；(2)临床实施，由患者自我报告的服药依从性定义 (2 a，2°结果)，出院后吸烟患者的PCP处方(2 b，2°) 结果)，以及处方是否与核磁共振匹配(2c，2°结果)；以及(3)卫生保健利用率和 现有数据库跟踪的死亡率(探索性)，包括全州范围的田纳西医院 放电数据系统和CMS数据。所有参与者将接受烟草使用方面的咨询和药物治疗。 研究人员在戒烟临床试验、精确医学、 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：这是第一个将尼古丁代谢纳入临床护理的大型随机对照试验，并可能 从根本上改变吸烟治疗的一般方法，进入精准医学时代。