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 美国东南部地区的吸烟率和吸烟导致的癌症发病率最高 死亡率在全国。吸烟的医疗补助和医疗保险（CMS）受益人吸烟的风险很高- 然而，每年只有不到五分之一的CMS登记吸烟者（不到十分之一 田纳西州医疗补助吸烟者）与药房福利接受戒烟药物。此外，委员会认为， 当提供戒烟药物时，它不是生物学上为最大功效而定制的。的比率 3-羟基可替宁与可替宁的比值（称为尼古丁代谢物比值（NMR））反映了CYP 2A 6活性， 尼古丁代谢率。在通过NMR评估的“正常”代谢者中，伐尼克兰产生戒断反应。 在6个月时，吸烟率大约是尼古丁贴片的两倍（23%对13%，p<0.05），而在“慢” 代谢者，戒烟率不因药物而异。需要治疗的人数，以帮助一个正常代谢者戒烟 吸烟对伐尼克兰的影响仅为4.9，对尼古丁贴片的影响为26，这为正常配对建立了科学前提。 代谢慢者用伐尼克兰，代谢慢者用尼古丁。我们建议测试代谢-知情 吸烟治疗（MIST），一种精确的方法，从生物学角度为尼古丁量身定制药物 代谢，为CMS受益人在中南部谁吸烟。我们假设MIST将是 上级于常规治疗（UC），即，选择药物不知情的核磁共振，戒烟。我们 将范德比尔特大学医学中心（VUMC）的81名每日吸烟的成年人随机分为MIST组和对照组。雾 NMR-药物匹配率增加3倍以上：未校正比值比3.67（95%置信区间 1.33-11.00; p值=0.02），患者高度可接受。评估MIST相对于 UC用于禁欲及其在临床实践中由患者和提供者使用，MIST RCT将招募1，000名 CMS入组的每日吸烟的成年人，他们住院并接受住院VUMC烟草咨询 治疗服务。具体目的是比较MIST与UC对以下方面的影响：（1）6岁时的禁欲 个月（1a，1°研究结果），定义为经生化验证的7天时点戒烟率，以及12 月（1b，2°结局）;（2）临床实施，由患者自我报告的药物依从性定义 (2a，2°结局），PCP为出院后吸烟患者开具的药物处方（2b，2° 结果），以及处方是否与核磁共振匹配（2c，2°结果）;和（3）医疗保健利用和 现有数据库（包括田纳西州医院）跟踪的死亡率（探索性） 出院数据系统和CMS数据。所有参与者都将接受烟草使用的咨询和药物治疗。 研究者在戒烟临床试验、精准医学、 吸烟药物基因组学和使用大型数据库，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RCT， 从根本上将吸烟治疗从一般方法转变为精确医学时代。