Coronary DiseasePhase 3BARI2DNCT00006305
Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes
A Phase 3 study testing Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions, Coronary Artery Bypass and Biguanides, thiazolidinediones in people with Coronary Disease and Cardiovascular Diseases, run by University of Pittsburgh.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Coronary Disease, Cardiovascular Diseases, Heart Diseases
- What is being tested?
- Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions, Coronary Artery Bypass and Biguanides, thiazolidinediones
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,368 participants
- Where
- No sites listed yet
- Study dates
- Sep 2000to Mar 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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%
Show all 26Show fewer
- 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:
- Exercise or pharmacologically-induced:
- 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
- Myocardial perfusion defect
- Myocardial wall motion abnormality
- 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
- 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.
About this study
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).
SPECIFIC AIMS
Read more
- Primary Aim
The primary aim of the BARI 2D trial is to test the following two hypotheses of treatment efficacy in 2400 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:
- 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;
- Method of Glycemic Control Hypothesis: with a target HbA1c level of less than 7.0%, a strategy of hyperglycemia management directed at insulin sensitization results in lower 5-year mortality compared to a strategy of insulin provision.
- 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.
Read the detailed description
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.
- Conditions
- Coronary Disease, Cardiovascular Diseases, Heart Diseases, Insulin Resistance, Diabetes Mellitus, Diabetes Mellitus, Non-Insulin-Dependent
- Being tested
- Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions, Coronary Artery Bypass, Biguanides, thiazolidinediones, Insulin, sulfonylurea, ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers
- Medical subject headings
- Coronary Disease, Cardiovascular Diseases, Heart Diseases, Insulin Resistance, Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventionsProcedure or surgery
Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions
Coronary Artery BypassProcedure or surgery
Coronary Artery Bypass
Biguanides, thiazolidinedionesDrug
Biguanides, thiazolidinediones
Insulin, sulfonylureaDrug
Insulin, sulfonylurea
ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel BlockersDrug
ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers
| Study group | Role | What they receive |
|---|---|---|
| Revascularization and Insulin Providing (IP) | Active comparator | Prompt revascularization with intensive medical therapy and insulin providing glycemic control strategy Receives: Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions; Procedure: Coronary Artery Bypass; Drug: Insulin, sulfonylurea; Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers |
| Revascularization and Insulin Sensitizing (IS) | Active comparator | Prompt revascularization with intensive medical therapy and insulin sensitizing glycemic control strategy Receives: Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions; Procedure: Coronary Artery Bypass; Drug: Biguanides, thiazolidinediones; Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers |
| Medical Therapy and Insulin Providing (IP) | Active comparator | Intensive medical therapy with delayed revascularization if clinically indicated and insulin providing glycemic control strategy Receives: Drug: Insulin, sulfonylurea; Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers |
| Medical Therapy and Insulin Sensitizing (IS) | Active comparator | Intensive medical therapy with delayed revascularization if clinically indicated and insulin sensitizing glycemic control strategy Receives: Drug: Biguanides, thiazolidinediones; Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With All-Cause Mortality
Measured: five years
Secondary outcomes (1)
Number of Participants With Death, Myocardial Infarction, or Stroke
Measured: five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2000 (estimated)
- Study startSep 2000
- Primary completionNov 2008
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (52)Papers the sponsor has linked to this study.
- Other trials for Coronary DiseaseStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 2,368 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Maria Mori Brooks, University of Pittsburgh
- Investigators
- Bernard Chaitman, MD, Principal investigator, St. Louis UniversityRobert L Frye, MD, Study chair, Mayo ClinicMark Hlatky, Principal investigator, Stanford UniversityBurton Sobel, Principal investigator, University of Vermont & State Agricultural CollegeSheryl F. Kelsey, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006305
- Sponsor's protocol ID
- 133
- Other IDs
- U01HL061744, U01HL061746, U01HL061748, U01HL063804
- Acronym
- BARI2D
- Status last verified
- Jan 2016
- First submitted
- 28 Sep 2000
- Last updated
- 8 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1161/01.cir.0000048897.03553.e4.
PubMed 12566379Brooks MM, Frye RL, Genuth S, Detre KM, Nesto R, Sobel BE, Kelsey SF, Orchard TJ; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial Investigators. Hypotheses, design, and methods for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. Am J Cardiol. 2006 Jun 19;97(12A):9G-19G. doi: 10.1016/j.amjcard.2006.02.023. Epub 2006 Apr 17.
PubMed 16813734Bypass Angioplasty Revascularization Investigation 2 Diabetes Study Group. Baseline characteristics of patients with diabetes and coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Am Heart J. 2008 Sep;156(3):528-536, 536.e1-5. doi: 10.1016/j.ahj.2008.05.015. Epub 2008 Jul 31.
PubMed 18760137BARI 2D Study Group; Frye RL, August P, Brooks MM, Hardison RM, Kelsey SF, MacGregor JM, Orchard TJ, Chaitman BR, Genuth SM, Goldberg SH, Hlatky MA, Jones TL, Molitch ME, Nesto RW, Sako EY, Sobel BE. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009 Jun 11;360(24):2503-15. doi: 10.1056/NEJMoa0805796. Epub 2009 Jun 7.
PubMed 19502645Brooks MM, Chung SC, Helmy T, Hillegass WB, Escobedo J, Melsop KA, Massaro EM, McBane RD, Hyde P, Hlatky MA; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. Health status after treatment for coronary artery disease and type 2 diabetes mellitus in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. Circulation. 2010 Oct 26;122(17):1690-9. doi: 10.1161/CIRCULATIONAHA.109.912642. Epub 2010 Oct 11.
PubMed 20937978Grogan M, Jenkins M, Sansing VV, MacGregor J, Brooks MM, Julien-Williams P, Amendola A, Abbott JD; BARI 2D Study Group. Health insurance status and control of diabetes and coronary artery disease risk factors on enrollment into the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Diabetes Educ. 2010 Sep-Oct;36(5):774-83. doi: 10.1177/0145721710374653. Epub 2010 Jun 28.
PubMed 20584997Wall BM, Hardison RM, Molitch ME, Marroquin OC, McGill JB, August PA; BARI 2D Study Group. High prevalence and diversity of kidney dysfunction in patients with type 2 diabetes mellitus and coronary artery disease: the BARI 2D baseline data. Am J Med Sci. 2010 May;339(5):401-10. doi: 10.1097/MAJ.0b013e3181d430ad.
PubMed 20375690Rana JS, Hardison RM, Pop-Busui R, Brooks MM, Jones TL, Nesto RW, Bourassa MG; BARI 2D Investigators. Resting heart rate and metabolic syndrome in patients with diabetes and coronary artery disease in bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial. Prev Cardiol. 2010 Summer;13(3):112-6. doi: 10.1111/j.1751-7141.2010.00067.x.
PubMed 20626665Thomas SB, Sansing VV, Davis A, Magee M, Massaro E, Srinivas VS, Helmy T, Desvigne-Nickens P, Brooks MM; BARI 2D Study Group. Racial differences in the association between self-rated health status and objective clinical measures among participants in the BARI 2D trial. Am J Public Health. 2010 Apr 1;100 Suppl 1(Suppl 1):S269-76. doi: 10.2105/AJPH.2009.176180. Epub 2010 Feb 10.
PubMed 20147671Hlatky MA, Chung SC, Escobedo J, Hillegass WB, Melsop K, Rogers W, Brooks MM; BARI 2D Study Group. The effect of obesity on quality of life in patients with diabetes and coronary artery disease. Am Heart J. 2010 Feb;159(2):292-300. doi: 10.1016/j.ahj.2009.11.004.
PubMed 20152229Albu JB, Lu J, Mooradian AD, Krone RJ, Nesto RW, Porter MH, Rana JS, Rogers WJ, Sobel BE, Gottlieb SH; BARI 2D Study Group. Relationships of obesity and fat distribution with atherothrombotic risk factors: baseline results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Obesity (Silver Spring). 2010 May;18(5):1046-54. doi: 10.1038/oby.2009.339. Epub 2009 Oct 29.
PubMed 19875998Hlatky MA, Boothroyd DB, Melsop KA, Kennedy L, Rihal C, Rogers WJ, Venkitachalam L, Brooks MM; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. Economic outcomes of treatment strategies for type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. Circulation. 2009 Dec 22;120(25):2550-8. doi: 10.1161/CIRCULATIONAHA.109.912709. Epub 2009 Nov 17.
PubMed 19920002Chaitman BR, Hardison RM, Adler D, Gebhart S, Grogan M, Ocampo S, Sopko G, Ramires JA, Schneider D, Frye RL; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. The Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: impact of treatment strategy on cardiac mortality and myocardial infarction. Circulation. 2009 Dec 22;120(25):2529-40. doi: 10.1161/CIRCULATIONAHA.109.913111. Epub 2009 Nov 17.
PubMed 19920001Kim LJ, King SB 3rd, Kent K, Brooks MM, Kip KE, Abbott JD, Jacobs AK, Rihal C, Hueb WA, Alderman E, Sing IR, Attubato MJ, Feit F; BARI 2D (Bypass Angioplasty Revascularization Investigation Type 2 Diabetes) Study Group. Factors related to the selection of surgical versus percutaneous revascularization in diabetic patients with multivessel coronary artery disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. JACC Cardiovasc Interv. 2009 May;2(5):384-92. doi: 10.1016/j.jcin.2009.01.009.
PubMed 19463459Schwartz L, Kip KE, Alderman E, Lu J, Bates ER, Srinivas V, Bach RG, Mighton LD, Feit F, King S 3rd, Frye RL; BARI 2D Study Group. Baseline coronary angiographic findings in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI 2D). Am J Cardiol. 2009 Mar 1;103(5):632-8. doi: 10.1016/j.amjcard.2008.11.024. Epub 2009 Jan 12.
PubMed 19231325
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00006305
- Acronym / sponsor ID
- BARI2D / 133
- Conditions
- Coronary Disease, Cardiovascular Diseases, Heart Diseases, Insulin Resistance, Diabetes Mellitus, Diabetes Mellitus, Non-Insulin-Dependent
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,368 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Sep 2000
- Primary completion
- Nov 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 29 Sep 2000 (estimated)
- Results
- Posted 12 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
SPECIFIC AIMS
- Primary Aim
The primary aim of the BARI 2D trial is to test the following two hypotheses of treatment efficacy in 2400 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:
- 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;
- Method of Glycemic Control Hypothesis: with a target HbA1c level of less than 7.0%, a strategy of hyperglycemia management directed at insulin sensitization results in lower 5-year mortality compared to a strategy of insulin provision.
- 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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Revascularization and Insulin Providing (IP) | Active comparator | Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions, Procedure: Coronary Artery Bypass, Drug: Insulin, sulfonylurea, Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel BlockersPrompt revascularization with intensive medical therapy and insulin providing glycemic control strategy |
| Revascularization and Insulin Sensitizing (IS) | Active comparator | Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions, Procedure: Coronary Artery Bypass, Drug: Biguanides, thiazolidinediones, Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel BlockersPrompt revascularization with intensive medical therapy and insulin sensitizing glycemic control strategy |
| Medical Therapy and Insulin Providing (IP) | Active comparator | Drug: Insulin, sulfonylurea, Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel BlockersIntensive medical therapy with delayed revascularization if clinically indicated and insulin providing glycemic control strategy |
| Medical Therapy and Insulin Sensitizing (IS) | Active comparator | Drug: Biguanides, thiazolidinediones, Drug: ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel BlockersIntensive medical therapy with delayed revascularization if clinically indicated and insulin sensitizing glycemic control strategy |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventionsAngioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions | Procedure or surgery | Revascularization and Insulin Providing (IP), Revascularization and Insulin Sensitizing (IS) |
| Coronary Artery BypassCoronary Artery Bypass | Procedure or surgery | Revascularization and Insulin Providing (IP), Revascularization and Insulin Sensitizing (IS) |
| Biguanides, thiazolidinedionesBiguanides, thiazolidinediones | Drug | Medical Therapy and Insulin Sensitizing (IS), Revascularization and Insulin Sensitizing (IS) |
| Insulin, sulfonylureaInsulin, sulfonylurea | Drug | Medical Therapy and Insulin Providing (IP), Revascularization and Insulin Providing (IP) |
| ACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel BlockersACE Inhibitors, Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers | Drug | Medical Therapy and Insulin Providing (IP), Medical Therapy and Insulin Sensitizing (IS), Revascularization and Insulin Providing (IP), Revascularization and Insulin Sensitizing (IS) |
Primary outcome
Number of Participants With All-Cause Mortality
Time frame: five years
1 secondary outcome
Number of Participants With Death, Myocardial Infarction, or Stroke
Time frame: five years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12566379Sobel 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. doi: 10.1161/01.cir.0000048897.03553.e4.
- Background: PubMed 16813734Brooks MM, Frye RL, Genuth S, Detre KM, Nesto R, Sobel BE, Kelsey SF, Orchard TJ; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial Investigators. Hypotheses, design, and methods for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. Am J Cardiol. 2006 Jun 19;97(12A):9G-19G. doi: 10.1016/j.amjcard.2006.02.023. Epub 2006 Apr 17.
- Background: PubMed 18760137Bypass Angioplasty Revascularization Investigation 2 Diabetes Study Group. Baseline characteristics of patients with diabetes and coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Am Heart J. 2008 Sep;156(3):528-536, 536.e1-5. doi: 10.1016/j.ahj.2008.05.015. Epub 2008 Jul 31.
- Background: PubMed 19502645BARI 2D Study Group; Frye RL, August P, Brooks MM, Hardison RM, Kelsey SF, MacGregor JM, Orchard TJ, Chaitman BR, Genuth SM, Goldberg SH, Hlatky MA, Jones TL, Molitch ME, Nesto RW, Sako EY, Sobel BE. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009 Jun 11;360(24):2503-15. doi: 10.1056/NEJMoa0805796. Epub 2009 Jun 7.
- Background: PubMed 20937978Brooks MM, Chung SC, Helmy T, Hillegass WB, Escobedo J, Melsop KA, Massaro EM, McBane RD, Hyde P, Hlatky MA; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. Health status after treatment for coronary artery disease and type 2 diabetes mellitus in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. Circulation. 2010 Oct 26;122(17):1690-9. doi: 10.1161/CIRCULATIONAHA.109.912642. Epub 2010 Oct 11.
- Background: PubMed 20584997Grogan M, Jenkins M, Sansing VV, MacGregor J, Brooks MM, Julien-Williams P, Amendola A, Abbott JD; BARI 2D Study Group. Health insurance status and control of diabetes and coronary artery disease risk factors on enrollment into the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Diabetes Educ. 2010 Sep-Oct;36(5):774-83. doi: 10.1177/0145721710374653. Epub 2010 Jun 28.
- Background: PubMed 20375690Wall BM, Hardison RM, Molitch ME, Marroquin OC, McGill JB, August PA; BARI 2D Study Group. High prevalence and diversity of kidney dysfunction in patients with type 2 diabetes mellitus and coronary artery disease: the BARI 2D baseline data. Am J Med Sci. 2010 May;339(5):401-10. doi: 10.1097/MAJ.0b013e3181d430ad.
- Background: PubMed 20626665Rana JS, Hardison RM, Pop-Busui R, Brooks MM, Jones TL, Nesto RW, Bourassa MG; BARI 2D Investigators. Resting heart rate and metabolic syndrome in patients with diabetes and coronary artery disease in bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial. Prev Cardiol. 2010 Summer;13(3):112-6. doi: 10.1111/j.1751-7141.2010.00067.x.
- Background: PubMed 20147671Thomas SB, Sansing VV, Davis A, Magee M, Massaro E, Srinivas VS, Helmy T, Desvigne-Nickens P, Brooks MM; BARI 2D Study Group. Racial differences in the association between self-rated health status and objective clinical measures among participants in the BARI 2D trial. Am J Public Health. 2010 Apr 1;100 Suppl 1(Suppl 1):S269-76. doi: 10.2105/AJPH.2009.176180. Epub 2010 Feb 10.
- Background: PubMed 20152229Hlatky MA, Chung SC, Escobedo J, Hillegass WB, Melsop K, Rogers W, Brooks MM; BARI 2D Study Group. The effect of obesity on quality of life in patients with diabetes and coronary artery disease. Am Heart J. 2010 Feb;159(2):292-300. doi: 10.1016/j.ahj.2009.11.004.
- Background: PubMed 19875998Albu JB, Lu J, Mooradian AD, Krone RJ, Nesto RW, Porter MH, Rana JS, Rogers WJ, Sobel BE, Gottlieb SH; BARI 2D Study Group. Relationships of obesity and fat distribution with atherothrombotic risk factors: baseline results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Obesity (Silver Spring). 2010 May;18(5):1046-54. doi: 10.1038/oby.2009.339. Epub 2009 Oct 29.
- Background: PubMed 19920002Hlatky MA, Boothroyd DB, Melsop KA, Kennedy L, Rihal C, Rogers WJ, Venkitachalam L, Brooks MM; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. Economic outcomes of treatment strategies for type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. Circulation. 2009 Dec 22;120(25):2550-8. doi: 10.1161/CIRCULATIONAHA.109.912709. Epub 2009 Nov 17.
- Click here for the BARI 2D Study Web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernard Chaitman, MD principal investigator
St. Louis University
Robert L Frye, MD study chair
Mayo Clinic
Mark Hlatky principal investigator
Stanford University
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions, Coronary Artery Bypass and Biguanides, thiazolidinediones in people with Coronary Disease and Cardiovascular Diseases, run by University of Pittsburgh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With All-Cause Mortality (time frame: five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006305, which also lists 52 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2016.