Comparative Effectiveness of Tirzepatide Versus Sitagliptin in Individuals at Cardiovascular Risk (TIRZSITA-CVOT)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 49,065
- 试验地点
- 1
- 主要终点
- Major adverse cardiovascular events
研究概览
简要总结
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
详细描述
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to assess the comparative effectiveness of tirzepatide vs sitagliptin as a placebo proxy, after the pivotal RCT SURPASS-CVOT (NCT04255433) and its emulation (NCT07088718) demonstrated non-inferiority, leaving both regulators and clinical guideline committees uncertain whether to approve and recommend tirzepatide for a cardiovascular indication. This comparative effectiveness target trial described below draws from eligibility criteria from the SURPASS-CVOT trial and its emulation. Although many features of the target trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice.
The purpose of this protocol is to specify the target trial assessing the comparative effectiveness of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1-RA) tirzepatide vs the dipeptidyl peptidase-4 inhibitors (DPP4i) sitagliptin on atherosclerotic cardiovascular end points in patients with type 2 diabetes and atherosclerotic cardiovascular disease.
The database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs sitagliptin in preventing atherosclerotic cardiovascular events. Clinical guidelines during the study period recommended both agents under investigation as second-line options for glucose lowering and were similarly costly.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of MI or stroke, surgical or percutaneous coronary/carotid peripheral artery revascularization, amputation, diagnosis of coronary/carotid/peripheral artery disease
- •BMI ≥25.0kg/m2
- •Type 2 diabetes
- •Age ≥40 years
- •Male or female sex
排除标准
- •Medullary thyroid carcinoma, MEN syndrome type 2, malignancy
- •Treatment for diabetic retinopathy/macular edema, heart failure NYHA IV, gastric emptying abnormality/bariatric surgery, end-stage renal disease or dialysis, pregnancy
- •Prior use of pramlintide or any GLP-1-RA except tirzepatide,
- •Pancreatitis, liver disease
- •Cardiovascular event or intervention, hospitalization for heart failure
- •Concurrent use of both drugs i.e. tirzepatide and sitagliptin
研究组 & 干预措施
Initiation of tirzepatide
Exposure group
干预措施: Initiation of tirzepatide (Drug)
Initiation of sitagliptin
Reference group
干预措施: Initiation of sitagliptin (Drug)
结局指标
主要结局
Major adverse cardiovascular events
时间窗: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, or all-cause mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
次要结局
- Composite of myocardial infarction or stroke(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- Myocardial infarction(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- Stroke(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- All-cause mortality(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- Composite of myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- Serious bacterial infections(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- Urinary tract infections(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
- Gastrointestinal adverse events(1 day after cohort entry date until the first of outcome or censoring, up to 365 days)
研究者
Shirley Vichy Wang
Associate Professor of Medicine
Brigham and Women's Hospital