Emulation of Effects of Injectable Semaglutide on Cardiovascular Outcomes in Individuals With Type 2 Diabetes: SUSTAIN6 Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 158,310
- 试验地点
- 1
- 主要终点
- Major adverse cardiac event (MACE), including myocardial infarction, stroke, and all cause death
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 RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to emulate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly emulated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not emulable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The SUSTAIN6 trial, is a non-inferiority trial to evaluate the effects of injectable semaglutide versus placebo in terms of cardiovascular safety (CV death, nonfatal MI, or nonfatal stroke) in patients with type 2 diabetes.
The database study designed to emulate SUSTAIN6 trial will be a new-user active comparative study, where we compare the effect of injectable semaglutide versus sitagliptin on MACE outcome among patients with T2DM. Sitagliptin was selected to act as an active-comparator proxy for placebo. Sitagliptin and the class of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated not to have an effect on MACE in a series of RCTs, and they are used in similar stages of disease/line of therapy as semaglutide, as well as being of similar cost.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes mellitus
- •Anti-diabetic drug naïve, or treated with one or two oral antidiabetic drug (OADs), or treated with human Neutral Protamin Hagedorn (NPH) insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OADs
- •Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease: prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50% stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, chronic heart failure - New York Heart Association (NYHA) class II-III, chronic renal impairment documents by estimated eGFR <60ml/min/1.73 m2 per MDRD
- •Age 60 years or older with subclinical evidence of cardiovascular disease. Subclinical cardiovascular risk factors as one of the following: persistent microalbuminuria (30-299mg/g) or proteinuria, ankle/brachial index less than 0.9
排除标准
- •Type 1 diabetes mellitus, secondary or gestational diabetes
- •Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening
- •Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening
- •Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness
- •Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening
- •History of chronic pancreatitis or idiopathic acute pancreatitis
- •Acute coronary or cerebro-vascular event within 90 days prior to randomization
- •Chronic heart failure New York Heart Association (NYHA) class IV
- •Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
- •Personal history of non-familial medullary thyroid carcinoma
- •Chronic hemodialysis or peritoneal dialysis
- •End stage liver disease
- •A prior solid organ transplant or awaiting solid organ transplant
- •Diagnosis of malignant neoplasm in the previous 5 years
- •Female of childbearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using an adequate contraceptive method
- •Known use of non-prescribed narcotics or illicit drugs
- •Proliferative retinopathy or maculopathy requiring treatment
- •Missing age or gender
- •Nursing home admission
研究组 & 干预措施
New use of semaglutide injection
Exposure group
干预措施: New use of semaglutide injection (Drug)
New initiation of sitagliptin
Reference group
干预措施: New initiation of sitagliptin (Drug)
结局指标
主要结局
Major adverse cardiac event (MACE), including myocardial infarction, stroke, and all cause death
时间窗: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Hazard ratio
次要结局
未报告次要终点
研究者
Shirley Vichy Wang
Associate Professor of Medicine
Brigham and Women's Hospital