Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Full description
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- 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 0.85.
3. Renal function: Estimated glomerular filtration rate at least 45 mL/min/1.73 m2.
4. Informed consent has been fully executed, and participant agrees to study procedures.
Exclusion criteria
- 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
Trial design
Primary purpose
Allocation
Interventional model
Masking
7,410 participants in 2 patient groups, including a placebo group
Trial contacts and locations
Loading...
Central trial contact
Gregory G Schwartz, PhD MD; Kevin Gropp
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal