Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion

Description

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.

Official Title

CSP #2002 - Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)

Details

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 one-year Pilot Phase trial from 2/2019 to 2/2020 and was approved for the full-scale trial, with projected full-scale launch in 10/2022.

Keywords

Prediabetic State Atherosclerosis Metformin Hemoglobin A, Glycosylated Coronary Artery Disease Peripheral Arterial Disease Cerebrovascular Disorders Metformin XR

Eligibility

You can join if…

Open to people ages 18 years and up

  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. At least one of these criteria must be met in the absence of diabetic treatment. For a participant to qualify with pre-diabetes on basis of one of these criteria, the results must have been obtained per the allowable time intervals indicated in Table 2. Any or all qualifying laboratory values may have been obtained either in a VA or a non-VA laboratory, but in either case the laboratory source documents, including date(s) of testing and test results must be available and data recorded on the appropriate case report form.
  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.
  3. Coronary artery disease: Fulfilled by at least one of (1), (2), or (3):
  4. History of myocardial infarction at least one month prior to Randomization:

Fulfilled by (a), (b), or both:

  1. Hospital summary or notes recording diagnosis of myocardial infarction
  2. At least two of the following:

i) pathologic Q-waves (and/or pathologic R wave in lead V1) consistent with myocardial infarction; ii) myocardial perfusion abnormality consistent with infarction; or iii) regional wall motion abnormality consistent with infarction.

(2) History of percutaneous coronary intervention or coronary artery bypass surgery at least one month prior to Randomization

(3) Angiographic evidence of significant coronary stenosis: At least 50% luminal stenosis in at least two major epicardial coronary arteries and/or their major branches (left main, left anterior descending and/or principal diagonal branches, left circumflex and/or principal obtuse marginal branches, or right and/or posterior descending or posterolateral branch).

b) Cerebrovascular disease: Fulfilled by at least one of criteria (1) through (4):

  1. Documented prior ischemic stroke (at least one month prior to Randomization) based upon at least one of the following:
  2. stroke documented in hospital discharge summary or neurologic consultation note, not including subarachnoid or subdural hemorrhage;
  3. neuroimaging study consistent with prior ischemic stroke
  4. Carotid artery stenosis 50% and history of transient ischemic attack or transient ischemic visual symptoms attributable to the identified lesion(s)
  5. Asymptomatic carotid stenosis 70%
  6. History of carotid revascularization (surgical or catheter-based)

c) Peripheral arterial disease: Fulfilled by (1), (2), or both:

  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 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.

You CAN'T join if...

  1. Related to glucometabolic state:
  2. 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.

  1. Treatment with systemic glucocorticoids within 3 months of randomization (due to potential effect on plasma glucose and HbA1c levels).
  2. 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.
  3. Related to safety or tolerability:

a) Metabolic acidosis (total CO2 below the local laboratory lower limit of normal on most recent blood chemistry panel)

b) Current treatment with cimetidine, vandetanib, or a systemic carbonic anhydrase inhibitor (topiramate, acetazolamide, methazolamide, dichlorphenamide, or zonisamide). Use of ophthalmic carbonic anhydrase inhibitors is not exclusionary.

c) Cirrhosis, active hepatitis, or jaundice at time of randomization, or total bilirubin > 2 times upper limit of normal on most recent laboratory study

d) Binge or heavy alcohol consumption within 6 months of randomization. Binge drinking is defined by consumption of 5 or more alcoholic drinks for men or 4 for women within 2 hours. Heavy drinking is defined by consumption of 5 or more alcoholic drinks on one occasion, occurring 5 or more times in a month.

e) Severe anemia (hemoglobin < 10 g/dL) on screening or most recent laboratory testing

f) Prior history of intolerance to metformin

  1. Related to likelihood of non-modifiable events:

a) Myocardial infarction, coronary revascularization procedure (PCI or CABG), or stroke within 1 month of randomization

b) Uncontrolled hypertension at screening assessment (systolic blood pressure 180 mm Hg or diastolic blood pressure 110 mm Hg

c) Acute or decompensated congestive heart failure

  1. Related to prognosis, reliability, ethics, or data validity:

a) Expected survival less than study duration

b) Participants considered to be unable, unwilling, or unreliable to meet protocol requirements

c) Impaired decision-making capacity, defined by any history of dementia or cognitive impairment

d) Concurrent participation in another research study involving a randomized comparison of drug or device treatments, unless specifically excepted by CSP.

  1. Female participants
  2. Pregnant or intent to become pregnant during the trial
  3. Lactating
  4. Women of childbearing potential who are not using a highly effective method of contraception

Locations

  • VA San Diego Healthcare System, San Diego, CA
    San Diego California 92161 United States
  • VA Loma Linda Healthcare System, Loma Linda, CA
    Loma Linda California 92357 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
VA Office of Research and Development
ID
NCT02915198
Phase
Phase 4 research study
Study Type
Interventional
Participants
Expecting 7410 study participants
Last Updated