BARI2DEfficacy of Revascularization and Medical Therapy in Type 2 Diabetes with Stable CAD
This study aims to evaluate the effectiveness of revascularization and medical therapy in treating type 2 diabetes with stable Coronary Artery Disease (CAD), focusing on the number of participants with all-cause mortality.
Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions
+ Coronary Artery Bypass
+ Insulin, sulfonylurea
Cardiovascular Diseases+10
+ Coronary Disease
+ Diabetes Mellitus
Treatment Study
Summary
Study start date: September 1, 2000
Actual date on which the first participant was enrolled.BACKGROUND: Type 2 diabetes mellitus, which is becoming more prevalent in our society as the population ages, is one of the strongest risk factors for coronary artery disease (CAD) and consequent mortality. In addition to generating an enormous toll in human suffering, diabetes places an economic burden approaching 100 billion dollars annually on the U.S. health care system. Despite the well known dismal prognosis of diabetes complicated by angiographically documented CAD, the optimal treatment paradigm for this large group of patients has not been studied. Coronary revascularization, while increasingly used, has not been directly shown to be of additional benefit to simultaneous intensive medical management of CAD along with management of hyperglycemia, hypertension, dyslipidemia, and other risk factors. Moreover, while intensive efforts to lower HbA1c have been demonstrated to favorably affect the clinical course of Type 2 diabetes mellitus in terms of microvascular complications, the optimal hyperglycemia management strategy with regard to macrovascular outcome is not known. These critical treatment dilemmas have motivated the development of BARI 2D, a multicenter randomized trial designed to determine in patients with Type 2 diabetes and stable CAD: 1) the efficacy of initial elective coronary revascularization combined with aggressive medical therapy, compared to an initial strategy of aggressive medical therapy alone; and 2) the efficacy of a strategy of providing more insulin (endogenous or exogenous), versus a strategy of increasing sensitivity to insulin (reducing insulin resistance), in the management of hyperglycemia, with a target HbA1c level of less than 7.0% for each strategy. DESIGN NARRATIVE: The BARI 2D trial is a multicenter study that uses a 2x2 factorial design, with 2400 patients being assigned at random to initial elective revascularization with aggressive medical therapy or aggressive medical therapy alone with equal probability, and simultaneously being assigned at random to an insulin providing or insulin sensitizing strategy of glycemic control (with a target value for HbA1c of less than 7.0% for all patients). Following confirmation of patient eligibility and provision of written consent, patients were randomized as shown below: Number of Patients Per Treatment Assignment (N=2400 patients in total) Stable Ischemic Heart Disease Treatment Strategy and Glycemic Control Strategy: Revascularization and Insulin Providing (IP) N=600; Revascularization and Insulin Sensitizing (IS) N=600; Medical and Insulin Providing (IP) N=600; Medical and and Insulin Sensitizing (IS) N=600.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.2368 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 25 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * Diagnosis of Type 2 diabetes mellitus * Coronary arteriogram showing one or more vessels amenable to revascularization (greater than or equal to 50% stenosis) * Objective documentation of ischemia OR subjectively documented typical angina with greater than or equal to 70% stenosis in at least one artery * Suitability for coronary revascularization by at least one of the available methods (does not require the ability to achieve complete revascularization) * Ability to perform all tasks related to glycemic control and risk factor management Exclusion Criteria: * Definite need for invasive intervention as determined by the attending cardiologist * Prior bypass surgery (CABG) or prior catheter-based intervention within the 12 months before study entry * Planned intervention for disease in bypass graft(s) if the patient is randomly assigned to a strategy of initial revascularization * Class III or IV CHF * Creatinine greater than 2.0 mg/dL * HbA1c greater than 13% * Need for major vascular surgery concomitant with revascularization (e.g., carotid endarterectomy) * Left main stenosis greater than or equal to 50% * Non-cardiac illness expected to limit survival * Hepatic disease (ALT greater than 2 times the ULN) * Fasting triglycerides greater than 1000 mg/dL in the presence of moderate glycemic control (HbA1c less than 9.0%) * Current alcohol abuse * Chronic steroid use judged to interfere with the control of diabetes, exceeding 10 mg of Prednisone per day or the equivalent * Pregnancy, known, suspected, or planned in 5 years after study entry * Geographically inaccessible or unable to return for follow-up * Enrolled in a competing randomized trial or clinical study * Unable to understand or cooperate with protocol requirements Patients with Type 2 diabetes mellitus and CAD documented by coronary arteriography will be eligible for the trial if revascularization is not required for prompt control of severe or unstable angina. Diabetic patients who are being treated with insulin or oral hypoglycemic drugs will be eligible as well as diabetic patients treated with diet and exercise alone provided that a diagnosis of diabetes can be confirmed by record review or that a fasting plasma glucose (FPG) greater than 125/mg/dL (7.0 mmol/L) can be obtained. The determination of suitability for BARI 2D will be made by a physician-investigator at each participating institution on clinical grounds at the time of coronary angiography. Significant CAD will be defined as at least one stenosis greater than 50%. Angina and ischemia will be assessed by use of patient self-report, physician examination, and appropriate diagnostic measures including exercise myocardial perfusion imaging, exercise echocardiography, exercise electrocardiography, and IV dipyridamole or adenosine myocardial perfusion imaging or invasively by doppler or pressure wire. Objective documentation of myocardial ischemia includes any of the following: 1. Exercise or pharmacologically-induced: 1. Greater than or equal to 1 mm of horizontal or downsloping ST depression or elevation for greater than or equal to 60-80 milliseconds after the end of the QRS complex 2. Myocardial perfusion defect 3. Myocardial wall motion abnormality 2. Stabilized, prior acute coronary syndrome with CK-MB or troponin elevation or with new, greater than or equal to 0.5 mm ST depression or elevation, or T wave inversion of greater than or equal to 3 mm in 2 contiguous ECG leads 3. Doppler or pressure wire showing coronary flow reserve (CFR) less than 2.0 or fractional flow reserve (FFR) less than 0.75 Among patients without documented ischemia, only patients with stenosis greater than or equal to 70% presenting with classic anginal symptoms will be eligible for randomization.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.4 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
Active ComparatorGroup II
Active ComparatorGroup III
Active ComparatorGroup IV
Active ComparatorStudy Objectives
Primary Objectives
Secondary Objectives