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Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02915198
Recruitment Status : Not yet recruiting
First Posted : September 26, 2016
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
This research will help us to learn if the medicine called metformin reduces the risk of death, heart attacks, and/or strokes in patients who have pre-diabetes and heart or blood vessel problems.

Condition or disease Intervention/treatment Phase
Prediabetic State Atherosclerosis Metformin Drug: Metformin XR Drug: Placebo Phase 4

Detailed 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 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.

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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)
Estimated Study Start Date : October 1, 2022
Estimated Primary Completion Date : September 30, 2028
Estimated Study Completion Date : September 30, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prediabetes

Arm Intervention/treatment
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.
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.
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





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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):

  1. History of myocardial infarction at least one month prior to randomization.
  2. History of percutaneous coronary intervention or coronary artery bypass surgery at least one month prior to randomization.
  3. 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):

  1. Documented prior ischemic stroke (at least one month prior to randomization),
  2. Carotid artery stenosis 50% and history of transient ischemic attack or transient ischemic visual symptoms attributable to the identified lesion(s),
  3. Asymptomatic carotid stenosis of at least 70% luminal diameter,
  4. History of carotid revascularization (surgical or catheter-based).

Peripheral arterial disease: Fulfilled by at least one of the following:

  1. History of aorto-iliac or peripheral artery intervention (surgical or catheter based) for limb ischemia, or amputation for limb ischemia,
  2. 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:

  1. 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.
  2. Treatment with systemic glucocorticoids within 3 months of randomization
  3. 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.
  4. Total CO2 below the local laboratory lower limit of normal on most recent blood chemistry panel
  5. Current treatment with cimetidine, vandetanib, or a systemic treatment with a carbonic anhydrase inhibitor.
  6. Cirrhosis, active hepatitis, or jaundice at time of randomization, or total bilirubin > 2 times upper limit of normal
  7. Binge or heavy alcohol consumption within 6 months of randomization
  8. Severe anemia (hemoglobin < 10 g/dL)
  9. Prior history of intolerance to metformin
  10. Myocardial infarction, coronary revascularization procedure, or stroke within 1 month of randomization
  11. Uncontrolled hypertension at screening assessment (systolic blood pressure 180 mm Hg or diastolic blood pressure 110 mm Hg
  12. Acute or decompensated congestive heart failure
  13. Expected survival less than study duration
  14. Participants considered to be unable, unwilling, or unreliable to meet protocol requirements
  15. Impaired decision-making capacity, defined by any history of dementia or cognitive impairment
  16. Concurrent participation in another research study involving a randomized comparison of drug or device treatments, unless specifically excepted.
  17. Pregnant, intent to become pregnant during the trial, or lactating
  18. Women of childbearing potential who are not using a highly effective method of contraception

Information from the National Library of Medicine

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


Contacts
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Contact: Gregory G Schwartz, PhD MD (720) 723-6070 Gregory.Schwartz@va.gov

Locations
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Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Study Chair: Gregory G. Schwartz, PhD MD Rocky Mountain Regional VA Medical Center, Aurora, CO
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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: June 24, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by VA Office of Research and Development:
Metformin
Atherosclerosis
Prediabetic State
Hemoglobin A, Glycosylated
Coronary Artery Disease
Peripheral Arterial Disease
Cerebrovascular Disorders
Additional relevant MeSH terms:
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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