Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes
Condition: Atherosclerosis
MeSH terms: Atherosclerosis
Intervention: Glipizide; rosiglitazone maleate
Intervention description: oral anti-diabetic medication; oral antidiabetic medication
Intervention MeSH terms: Rosiglitazone; Glipizide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 672.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: atheroma; IVUS; Intravascular ultrasound; atherosclerosis

Summary:

      The purpose of this study is to test the safety and effectiveness of rosiglitazone against a
      sulfonylurea in reducing or slowing the development of atherosclerosis in the blood vessels
      of the heart.
    

Eligibility criteria:

        Inclusion criteria:

          -  Male or female between 30 to 80 years of age, inclusive.

          -  Established diagnosis of T2DM (based on diagnostic criteria of the American Diabetes
             Association (ADA), WHO guidelines or local national guidelines).

          -  Subjects who are undergoing coronary angiography for evaluation of suspected or
             previously diagnosed coronary artery disease or who are undergoing PCI.

          -  Subjects' prior anti-hyperglycemic diabetic therapy:

        Diet and exercise only (drug naïve), with HbA1c >7.0 and £ 10.0%. HbA1c > 6.5 and <= 8.5%.

          -  Left ventricular ejection fraction (EF) ³ 40% as assessed by contrast ventriculography
             (or previously documented in medical notes within one month prior to index procedure
             by other methods e.g. echocardiography or nuclear study)

          -  Female subjects must be postmenopausal (i.e., >6 months without menstrual period),
             surgically sterile, or using effective contraceptive measures (oral contraceptives,
             Norplant, Depo-Provera, an intra-uterine device (IUD), a diaphragm with spermicide or
             a condom with spermicide). Women of childbearing potential must use effective
             contraceptive measures for at least 1 month prior to visit 1a, and should continue to
             use the same contraceptive method during the study and for 30 days after discontinuing
             study medication.

          -  Willingness and ability to give informed consent prior to entering the study and
             available to complete the study.

        Exclusion Criteria:

          -  Type 1 diabetes and/or history of diabetic ketoacidosis.

          -  Exposure to a TZD or other PPAR-g agonist within the 6 months prior to screening
             visit.

          -  Subjects treated with triple OAD therapy or high dose dual combination OAD therapy
             [1].

          -  Subjects who have required chronic insulin use in the last 6 months (except during
             pregnancy or acute episodes such as hospitalization, trauma or infection).

          -  ST segment elevation myocardial infarction in the last 30 days.

          -  Subjects who have a history or are scheduled to receive coronary artery bypass graft
             surgery (CABG), valve repair or replacement, aneurysmectomy or planned major
             non-cardiac surgery during the study period.

          -  Subjects who have severe cardiac valvular disease

          -  Stroke or resuscitated in the past 6 months

          -  History of congestive heart failure (NYHA class I - IV)

          -  History of significant hypersensitivity or reaction (e.g., difficulty swallowing,
             difficulty breathing, tachycardia or skin reaction) to any TZD, SU, biguanide or
             insulin

          -  Prior history of severe edema or edema requiring medical treatment.

          -  Chronic disease requiring chronic or intermittent treatment with oral, intravenous, or
             injected corticosteroids (use of topical, inhaled, or nasal corticosteroids is
             permissible).

          -  Recent history or suspicion of current drug abuse or alcohol abuse within the last 6
             months.

          -  Untreated hypo- or hyperthyroidism

          -  A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or
             adequately treated cervical carcinoma in situ) in the past 3 years or current
             treatment for the active cancer.

          -  Any clinically significant abnormality identified at the screening visit, physical
             examination, laboratory tests, or electrocardiogram which, in the judgement of the
             Investigator, would preclude safe completion of the study.

          -  Blood pressure: SBP >170 or DBP > 100 mmHg

          -  Significant anemia (Hemoglobin < 11 g/dL for males and < 10 g/dL for females).

          -  Significant renal disease manifested by serum creatinine (> 1.5mg/dL for males or >
             1.4mg/dL for females), or where the use of metformin is contra-indicated.

          -  Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation
             (ALT or AST > 2.5 times upper limit of normal (ULN) or bilirubin >2x ULN).

          -  History of myopathy or history of elevated creatine kinase (CK) > 3 times upper normal
             limit.

          -  Use of an investigational drug within 30 days or 5 half-lives (whichever is the
             longer).

          -  Women who are lactating, pregnant or planning to become pregnant during the course of
             the study.

          -  Unwillingness or inability to comply with the procedures described in this protocol.