Insulin Resistance Intervention After Stroke Trial
Condition: Stroke; Myocardial Infarction; Diabetes
MeSH terms: Stroke; Myocardial Infarction; Insulin Resistance; Infarction
Intervention: pioglitazone; placebo
Intervention description: a thiazolidinedione drug; an inactive substance
Intervention MeSH terms: Pioglitazone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 3876.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: stroke; heart attack; diabetes; pioglitazone; insulin resistance

Summary:

      The purpose of this study is to determine if pioglitazone is effective in preventing future
      strokes or heart attacks among non-diabetic persons who have had a recent ischemic stroke.
    

Eligibility criteria:

        Inclusion Criteria

          1. Ages 40 years or greater at the time of randomization.

          2. Ischemic stroke or TIA no less than 14 days and no more than 6 months before
             randomization

          3. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis
             Model Assessment of insulin sensitivity (HOMA).

          4. Both ability and willingness to provide informed consent.

          5. Presence of none of the exclusion criteria.

        Exclusion Criteria

        Permanent Exclusions

          1. Severely disabling stroke as indicated by an inability to participate in scheduled
             follow-up activities.

          2. Persons whose ischemic stroke or TIA was related to structural cardiac lesion,
             significant head trauma, proximal arterial dissection or medical instrumentation.

          3. Diabetes mellitus as defined by recent use of medication for diabetes as an
             out-patient (*see note below) or two fasting plasma blood sugars > 126 mg/dL.

          4. HgbA1c > 7.0%.

          5. Irreversible medical conditions likely to affect short-term survival or ability to
             participate in the study protocol. These include:

               -  Cancer or other chronic disease with poor prognosis (predicted survival of less
                  than four years).

               -  Severe neurologic or psychiatric disease that would complicate the evaluation of
                  study outcomes (e.g., dementia or schizophrenia).

          6. History of intolerance to any thiazolidinedione.

          7. Pregnancy or desire to become pregnant.

          8. Oral contraceptive use.

          9. Ongoing use of oral corticosteroids.

         10. History of heart failure

         11. Active liver disease as defined by known liver disease accompanied by cirrhosis,
             significant cholestasis, portal hypertension, hepatic encephalopathy, hepatic
             synthetic dysfunction, or expected significant loss of liver function over the course
             of the study.

         12. History of bladder cancer.

         13. Current participation in a conflicting clinical trial. A conflicting clinical trial is
             defined as a trial with any of following:

               -  Intervention that is known to affect the incidence of stroke or myocardial
                  infarction.

               -  Intervention that is an experimental drug.

               -  Outcome that includes stroke or myocardial infarction.

               -  Exclusion for participation in another trial.

        Temporary Exclusions Persons with temporary exclusions may be enrolled as soon as the
        exclusion has resolved.

          1. Alanine aminotransferase (ALT) >2.5 times the upper limit of normal.

          2. Hemoglobin <8.5 g/dl.

          3. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4).

          4. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2
             weeks following procedure).