CSP #2002 - Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 7,410
- 试验地点
- 40
- 主要终点
- Time in days to death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina, or symptom-driven coronary revascularization
研究概览
简要总结
This research will help us to learn if the medicine called metformin reduces the risk of death, heart attacks, and/or strokes in Veterans who have pre-diabetes and heart or blood vessel problems.
详细描述
CSP #2002 is a multicenter, prospective, randomized, double blind, secondary prevention trial to test the hypothesis that treatment with metformin, compared with placebo, reduces mortality and cardiovascular morbidity in Veterans with pre-diabetes and established atherosclerotic cardiovascular disease. Qualifying patients have pre-diabetes defined by HbA1c, fasting blood glucose, or oral glucose tolerance test criteria; clinically evident coronary, cerebrovascular, or peripheral arterial atherosclerotic cardiovascular disease; and estimated glomerular filtration rate of at least 45 mL/min/1.73 m2; and do not fulfill any exclusion criteria. Patients who are eligible and agree to participate are randomly assigned to treatment with metformin XR (titrated to a maximum dose of 2000 mg daily based on safety and tolerability) or matching placebo. All patients receive counseling on therapeutic lifestyle recommendations.
CSP #2002 had a Pilot Phase trial from 2/2019 to 1/2021 and was approved for the full-scale trial, with Full-scale study launch in 04/2023.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pre-diabetes: This condition is fulfilled by HbA1c of at least 5.7%, but less than 6.5%; or two measurements of fasting plasma glucose (on separate days) of 100-125 mg/dL; or a 2-hour plasma glucose level of 140-199 mg/dL following a 75 g glucose load oral glucose tolerance test.
- •Established atherosclerotic cardiovascular disease: Qualifying participants must have evidence of atherosclerotic disease in at least one of the following vascular beds: coronary, cerebrovascular, or peripheral arterial circulation.
- •Coronary artery disease is fulfilled by at least one of (1), (2), or (3):
- •History of myocardial infarction at least one month prior to randomization.
- •History of percutaneous coronary intervention or coronary artery bypass surgery at least one month prior to randomization.
- •Angiographic evidence of coronary stenosis of at least 50% in at least two major epicardial coronary arteries.
- •Cerebrovascular disease is fulfilled by at least one of criteria (1) through (4):
- •Documented prior ischemic stroke (at least one month prior to randomization),
- •Carotid artery stenosis 50% and history of transient ischemic attack or transient ischemic visual symptoms attributable to the identified lesion(s),
- •Asymptomatic carotid stenosis of at least 70% luminal diameter,
- •History of carotid revascularization (surgical or catheter-based).
- •Peripheral arterial disease: Fulfilled by at least one of the following:
- •History of aorto-iliac or peripheral artery intervention (surgical or catheter based) for limb ischemia, or amputation for limb ischemia,
- •Symptoms of intermittent claudication with ankle:brachial index less than or equal to 0.
- •3. Renal function: Estimated glomerular filtration rate at least 45 mL/min/1.73 m
- •4. Informed consent has been fully executed, and participant agrees to study procedures.
排除标准
- •Treatment with metformin or other anti-diabetic medication within 12 months of randomization. Note: In the absence of a diagnosis of diabetes, inpatient treatment with insulin or treatment with an SGLT2 inhibitor (e.g., for heart failure) or a GLP-1 receptor agonist (e.g., for obesity) is not exclusionary.
- •Treatment with systemic glucocorticoids within 3 months of randomization
- •Fasting plasma glucose greater than 130 mg/dL measured between screening and randomization visits, or any plasma glucose 180 mg/dL or HbA1c 7.0% measured within 12 months of randomization.
- •Total CO2 below the local laboratory lower limit of normal on most recent blood chemistry panel
- •Current treatment with cimetidine, vandetanib, or a systemic treatment with a carbonic anhydrase inhibitor.
- •Cirrhosis, active hepatitis, or jaundice at time of randomization, or total bilirubin > 2 times upper limit of normal
- •Binge or heavy alcohol consumption within 6 months of randomization
- •Severe anemia (hemoglobin < 10 g/dL)
- •Prior history of intolerance to metformin
- •Myocardial infarction, coronary revascularization procedure, or stroke within 1 month of randomization
- •Uncontrolled hypertension at screening assessment (systolic blood pressure 180 mm Hg or diastolic blood pressure 110 mm Hg
- •Acute or decompensated congestive heart failure
- •Expected survival less than study duration
- •Participants considered to be unable, unwilling, or unreliable to meet protocol requirements
- •Impaired decision-making capacity, defined by any history of dementia or cognitive impairment
- •Concurrent participation in another research study involving a randomized comparison of drug or device treatments, unless specifically excepted.
- •Pregnant, intent to become pregnant during the trial, or lactating
- •Women of childbearing potential who are not using a highly effective method of contraception
研究组 & 干预措施
Metformin
Participants receive initial treatment with metformin XR 500 mg 1 tablet daily, with stepwise titration to a maximum dose of 2000 mg (4 tablets) daily.
干预措施: Metformin XR (Drug)
Placebo
Participants receive initial treatment with 1 tablet daily of placebo (for metformin XR), with stepwise titration to a maximum of 4 tablets daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Time in days to death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina, or symptom-driven coronary revascularization
时间窗: through study completion, an average of 4.5 years
The primary outcome measure is the time to first occurrence of death, non-fatal myocardial infarction or stroke, hospitalization for unstable angina with objective evidence of acute myocardial ischemia, or coronary revascularization driven by acute or progressive symptoms.
次要结局
- Time in days to Cardiovascular Outcomes(through study completion, an average of 4.5 years)
- Time in days to Oncologic Outcome(through study completion, an average of 4.5 years)
- Time in days to Diabetes Outcome(through study completion, an average of 4.5 years)