Clinical Trial: Bypass Angioplasty Revascularization Investigation in Type 2 Diabetics (BARI 2D)

This study is currently recruiting patients.

Sponsors and Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The BARI 2D trial is a multicenter study that uses a 2x2 factorial design, with 2800 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 <7.0% for all patients). SPECIFIC AIMS

A. Primary Aim

The primary aim of the BARI 2D trial is to test the following two hypotheses of treatment efficacy in 2800 patients with Type 2 diabetes mellitus and documented stable CAD, in the setting of uniform glycemic control and intensive management of all other risk factors including dyslipidemia, hypertension, smoking, and obesity:

1. Coronary Revascularization Hypothesis: a strategy of initial elective revascularization of choice (surgical or catheter-based) combined with aggressive medical therapy results in lower 5-year mortality compared to a strategy of aggressive medical therapy alone;

2. Method of Glycemic Control Hypothesis: with a target HbA1c level of <7.0%, a strategy of hyperglycemia management directed at insulin sensitization results in lower 5-year mortality compared to a strategy of insulin provision.

B. Secondary Aims

The secondary aims of the BARI 2D trial include: a) comparing the death, myocardial infarction or stroke combined endpoint event rate between the revascularization versus medical therapy groups and between the insulin sensitization versus insulin provision groups; b) comparing rates of myocardial infarction, other ischemic events, angina and quality of life associated with each revascularization and hyperglycemia management strategy; c) evaluating the relative economic costs associated with the trial treatment strategies, d) exploring the effect of glycemic control strategy on the progression and mechanism of vasculopathy including changes in PAI-1 gene expression.

Condition Treatment or Intervention Phase
Coronary Disease
Cardiovascular Diseases
Heart Diseases
Insulin Resistance
Diabetes Mellitus
Diabetes Mellitus, non-insulin dependent
 Procedure: Angioplasty, Transluminal, Percutaneous Coronary
 Procedure: Coronary Artery Bypass
 Drug: Hypoglycemic Agents
Phase III

MedlinePlus related topics:  Coronary Disease;   Diabetes;   Heart Diseases;   Heart Diseases--Prevention;   Metabolic Syndrome X;   Vascular Diseases

Study Type: Interventional
Study Design: Treatment, Randomized, Factorial Assignment

Further Study Details: 

Study start: September 2000;  Expected completion: June 2007

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 < 7.0% for each strategy.

DESIGN NARRATIVE: The BARI 2D trial is a multicenter study that will use a 2x2 factorial design, with 2800 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 <7.0% for all patients). Following confirmation of patient eligibility and provision of written consent, patients will be randomized as shown below:

Number of Patients Per Treatment Assignment Revascularization Strategy

Revascularization Medical

Glycemic Control Strategy Insulin Providing (IP) 700 700

Insulin Sensitizing (IS) 700 700

Eligibility

Genders Eligible for Study:  Both

Criteria

Inclusion Criteria for BARI 2D 1. Diagnosis of Type 2 diabetes mellitus. 2. Coronary arteriogram showing one or more vessels amenable to revascularization (=50% stenosis). 3. Objective documentation of ischemia OR subjectively documented typical angina with =70% stenosis in at least one artery. 4. Suitability for coronary revascularization by at least one of the available methods (does not require the ability to achieve complete revascularization). 5. Ability to perform all tasks related to glycemic control and risk factor management. 6. Age 25 or older. 7. Informed written consent.

Exclusion Criteria for BARI 2D 1. Definite need for invasive intervention as determined by the attending cardiologist. 2. Prior bypass surgery (CABG) or prior catheter-based intervention within the past 12 months. 3. Planned intervention for disease in bypass graft(s) if the patient is randomized to a strategy of initial revascularization. 4. Class III or IV CHF. 5. Creatinine > 2.0 mg/dl. 6. HbA1c > 13%. 7. Need for major vascular surgery concomitant with revascularization (e.g., carotid endarterectomy). 8. Left main stenosis > 50%. 9. Non-cardiac illness expected to limit survival. 10. Hepatic disease (ALT> 2 times the ULN). 11. Fasting triglycerides > 1000 mg/dl in the presence of moderate glycemic control (HbA1c <9.0%). 12. Current alcohol abuse. 13. Chronic steroid use judged to interfere with the control of diabetes, exceeding 10 mg. of Prednisone per day or the equivalent. 14. Pregnancy, known, suspected, or planned in next 5 years. 15. Geographically inaccessible or unable to return for follow-up. 16. Enrolled in a competing randomized trial or clinical study. 17. 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)>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 >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, 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:

a. =1 mm of horizontal or downsloping ST depression or elevation for =60-80 milliseconds after the end of the QRS complex; b. myocardial perfusion defect; c. myocardial wall motion abnormality.

2. Stabilized, prior acute coronary syndrome with CK-MB or troponin elevation or with new, =0.5 mm ST depression or elevation, or T wave inversion of =3 mm in 2 contiguous ECG leads.

3. Doppler or pressure wire showing coronary flow reserve (CFR) <2.0 or fractional flow reserve (FFR) <0.75.

Among patients without documented ischemia, only patients with stenosis = 70% presenting with classic anginal symptoms will be eligible for randomization.


Location and Contact Information


Alabama
      University of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States; Recruiting
Roberta Hill, RN  205-934-7661    bhill@cardio.dom.uab.edu 
David Bell,  Study Chair

Illinois
      Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
Lorene Eckman, RN  312-926-5421    leckman@nmh.org 
Unknown,  Study Chair

Maryland
      University of Maryland Hospital, Baltimore,  Maryland,  21201,  United States; Recruiting
Warren Laskey, MD  410-328-2058    wlaskey@medicine.umaryland.edu 
Unknown,  Study Chair

      University of Maryland Hospital, Baltimore,  Maryland,  21201,  United States; Recruiting
Thomas Donner  410-328-6542    tdonner@medicine.umaryland.edu 
Unknown,  Study Chair

Massachusetts
      Lahey Clinic Medical Center, Burlington,  Massachusetts,  01805,  United States; Recruiting
Lisa Abel  781-744-8885    Lisa.Abel@lahey.org 
Unknown,  Study Chair

      Boston Medical Center, Boston,  Massachusetts,  02118,  United States; Recruiting
Deb Gannon, MS  617-638-8751    deborah.gannon@bmc.org 
Unknown,  Study Chair

Michigan
      Saint Joseph Mercy Hospital, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Penny Wilms, BSN  734-712-5675    wilmsp@trinity-health.org 
Unknown,  Study Chair

      Henry Ford Hospital Systems, Detroit,  Michigan,  48202,  United States; Recruiting
Raquel Pangilinan, RN  313-916-4268    rpangil1@hfhs.org 
Unknown,  Study Chair

Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Julie Dicken, RN  612-625-9477    dicke022@tc.umn.edu 
Unknown,  Study Chair

Missouri
      Mid America Heart Institute, Kansas City,  Missouri,  64111,  United States; Recruiting
Aimee Long, RN, BSN  816-932-5719    along@saint-lukes.org 
Unknown,  Study Chair

      Saint Louis University Health Sciences Center, St. Louis,  Missouri,  63110,  United States; Recruiting
Sharon Plummer, RN, CS, GNP  314-977-7536    plummere@slu.edu 
Unknown,  Study Chair

New York
      New York Medical College/Westchester Medical Center, Valhalla,  New York,  10595,  United States; Recruiting
Jane Rainaldi, RN  914-493-8815    rainaldij@cloud9.net 
Unknown,  Study Chair

      New York University School of Medicine, New York,  New York,  10016,  United States; Recruiting
Susan Cotton, RN  212-263-7224    susan.cotton@med.nyu.edu 
Unknown,  Study Chair

      Saint Lukes-Roosevelt Hospital Center, New York,  New York,  10025,  United States; Recruiting
Jeanine Albu, MD  212-523-4183    jba@columbia.edu 
Unknown,  Study Chair

Ohio
      Ohio State University Medical Center, Columbus,  Ohio,  43210,  United States; Recruiting
Cecilia Casey Boyer, RN, MS,  614-292-3177    boyer-1@medctr.ohio-state.edu 
Unknown,  Study Chair

Pennsylvania
      University of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Glory Koerbel, MSN, RN, CDE  412-383-8703    koerbelg@msx.dept-med.pitt.edu 
Unknown,  Study Chair

Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
Bella Belleza-Bascon  713-394-6917    kmaresh@bcm.tmc.edu 
Alan Garber,  Study Chair

      University of Texas Health Science Center, San Antonio, San Antonio,  Texas,  78251,  United States; Recruiting
Robin Prescott, NP  210-617-5300    prescott.robin@san-antonio.va.gov 
Unknown,  Study Chair

Vermont
      Fletcher Allen Health Care, Burlington,  Vermont,  05401,  United States; Recruiting
Michaelanne Rowen, RN, CCRC  802-847-4746    michaelanne.rowen@vtmednet.org 
Unknown,  Study Chair

Virginia
      University of Virginia, Charlottesville,  Virginia,  22908,  United States; Recruiting
Karen Murie, RN  434-982-1058    krm3x@virginia.edu 
Unknown,  Study Chair

Canada, Ontario
      University of Ottawa Heart Institute, Ottawa,  Ontario,  K1Y 4W7,  Canada; Recruiting
Melody Dallaire  (613) 761-5208    mdallaire@ottawaheart.ca 
Unknown,  Study Chair

Canada, Quebec
      Montreal Heart Institute, Montreal,  Quebec,  Canada; Recruiting
Johanne Trudel, RN  (514) 376-3330    jotrudel@icm.umontreal.ca 
Unknown,  Study Chair

      Quebec Heart Institute/Laval Hospital, Sainte-Foy,  Quebec,  G1V 4G5,  Canada; Recruiting
Giles Dagenais, MD  (418) 656-8711 
Unknown,  Study Chair

Study chairs or principal investigators

Bernard Chaitman,  St. Louis University   
Katherine Detre,  University of Pittsburgh   
Mark Hlatky,  Stanford University   
Burton Sobel,  University of Vermont & State Agricultural College   

More Information

http://www.bari2d.org/

Publications

Sobel BE, Frye R, Detre KM; Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial. Burgeoning dilemmas in the management of diabetes and cardiovascular disease: rationale for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. Circulation. 2003 Feb 4;107(4):636-42. Review.

Study ID Numbers:  133
Record last reviewed:  March 2005
Last Updated:  March 17, 2005
Record first received:  September 28, 2000
ClinicalTrials.gov Identifier:  NCT00006305
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005