Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)
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ClinicalTrials.gov Identifier: NCT02915198 |
Recruitment Status :
Recruiting
First Posted : September 26, 2016
Last Update Posted : January 8, 2024
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Condition or disease | Intervention/treatment | Phase |
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Prediabetic State Atherosclerosis Metformin | Drug: Metformin XR Drug: Placebo | Phase 4 |
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 patients 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 projected full-scale launch in 10/2022.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 7410 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | CSP #2002 - Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT) |
Actual Study Start Date : | April 3, 2023 |
Estimated Primary Completion Date : | March 31, 2029 |
Estimated Study Completion Date : | March 31, 2029 |
Arm | Intervention/treatment |
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Experimental: 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.
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Drug: Metformin XR
The study medication dose may be increased by a step-wise fashion up to a maximum of 4 tablets per day. |
Placebo Comparator: Placebo
Participants receive initial treatment with 1 tablet daily of placebo (for metformin XR), with stepwise titration to a maximum of 4 tablets daily.
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Drug: Placebo
For patients < 80 years of age at the time of a study visit, and with most recent eGFR 45 mL/min/1.73 m2, study medication dose may be increased in a stepwise fashion to a maximum of 4 tablets daily, corresponding to metformin XR 2000 mg or matching placebo. For patients 80 years of age or with most recent 30 eGFR < 45 mL/min/1.73 m2, the maximum dose of study medication is 2 tablets daily, corresponding to metformin XR 1000 mg or matching placebo |
- Time in days to death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina, or symptom-driven coronary revascularization [ Time Frame: 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.
- Time in days to Cardiovascular Outcomes [ Time Frame: through study completion, an average of 4.5 years ]
- Time to first occurrence of death, myocardial infarction, or stroke
- Time to first occurrence of a primary endpoint event, peripheral arterial disease event, or hospitalization for congestive heart failure
- Cumulative incidence of all components of the primary endpoint, including recurrent or multiple events in the same participant
- Cumulative incidence and time to first occurrence of each component of the primary outcome measure, peripheral arterial disease events, and hospitalization for congestive heart failure
- Time in days to Oncologic Outcome [ Time Frame: through study completion, an average of 4.5 years ]Time to new or recurrent diagnosis of a malignancy or death from a malignancy
- Time in days to Diabetes Outcome [ Time Frame: through study completion, an average of 4.5 years ]Time to new diagnosis of type 2 diabetes
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 140 mg/dL measured between screening and randomization visits, or any plasma glucose 200 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915198
Contact: Gregory G Schwartz, PhD MD | (720) 723-6070 | Gregory.Schwartz@va.gov |
Study Chair: | Gregory G. Schwartz, PhD MD | Rocky Mountain Regional VA Medical Center, Aurora, CO |
Responsible Party: | VA Office of Research and Development |
ClinicalTrials.gov Identifier: | NCT02915198 |
Other Study ID Numbers: |
2002 |
First Posted: | September 26, 2016 Key Record Dates |
Last Update Posted: | January 8, 2024 |
Last Verified: | January 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Metformin Atherosclerosis Prediabetic State Hemoglobin A, Glycosylated |
Coronary Artery Disease Peripheral Arterial Disease Cerebrovascular Disorders |
Atherosclerosis Prediabetic State Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Cardiovascular Diseases Diabetes Mellitus |
Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Metformin Hypoglycemic Agents Physiological Effects of Drugs |