Insulin resistance in patients who have had a stroke or transient ischaemic attack
Conditions
Interventions
Trade Name: ACTOS
Product Name: Pioglitazone hydrochloride
Pharmaceutical Form: Tablet
INN or Proposed INN: Pioglitazone hydrochloride
CAS Number: 112529-15-4
Concentration unit: mg milligram(s)
Conce
Sponsors
Yale University School of Medicine
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria a. Ages 40 years or greater at the time of randomization. b. Ischemic stroke or TIA no less than 14 days and no more than 6 months before randomization c. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis Model Assessment of insulin sensitivity (HOMA). d. Both ability and willingness to provide informed consent. e. Presence of none of the exclusion criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: Permanent Exclusions a. Severely disabling stroke as indicated by an inability to participate in scheduled follow-up activities. b. Persons whose ischemic stroke or TIA was related to structural cardiac lesion, significant head trauma, proximal arterial dissection or medical instrumentation. c. 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. d. HgbA1c >= 7.0%. e. 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). f. History of intolerance to any thiazolidinedione. g. Pregnancy, desire to become pregnant, or currently breastfeeding. h. Oral or estrogen patch contraceptive use. i. Ongoing use of oral corticosteroids. j. History of heart failure (includes patients with current or previous NYHA class I-4 heart failure). k. 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. l. History of bladder cancer. m. High risk for bladder cancer (i.e., current investigated macroscopic hematuria, history of cyclophosphamide exposure, or history of irradiation of the pelvic region) n. 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. a. ALT >2.5 times the upper limit of normal. b. Hemoglobin <8.5 g/dl. c. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4). d. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2 weeks following procedure). *Patients who have taken a medication to treat diabetes in the prior 3 months as an out-patient will not be eligible for participation. However, a patient who has recently taken a diabetes medication while hospitalized or for a reason other than diabetes (e.g., for impaired glucose tolerance), may be tested for eligibility after at least 7 days off the medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if pioglitazone, compared to placebo, will reduce the overall risk for fatal or non-fatal stroke or fatal or non-fatal myocardial infarction (MI) among non-diabetic men and women aged 40 years or older with insulin resistance, who have experienced a recent stroke or transient ischaemic attack (TIA). The sponsor hypothesizes that, among non-diabetics with insulin resistance, pioglitazone will reduce the rate of occurrence of any main outcome (fatal or non-fatal stroke or MI) within four years from 27% to 22%.;Secondary Objective: To determine if pioglitazone, compared to placebo, will: 1. Reduce the risk for stroke alone. 2. Reduce the risk for acute MI or unstable angina. 3. Prevent progression to overt diabetes. 4. Reduce the risk for all-cause mortality. 5. Reduce the risk for cognitive decline. 6. Reduce the risk for stroke, MI or episodes of CHF (combined). ;Primary end point(s): Rate of occurrence of fatal or non-fatal stroke or MI (i.e. % of patients in whom one or more of the events occur);Timepoint(s) of evaluation of this end point: After last patient last visit 2015 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine if pioglitazone, compared to placebo, will reduce the risk for stroke and will reduce the risk for acute coronary syndromes To determine if pioglitazone, compared to placebo, is effective in preventing progression to overt diabetes.;Timepoint(s) of evaluation of this end point: After last patient last visit 2015 | — |
Countries
Australia, Canada, Germany, Israel, Italy, United Kingdom, United States
Contacts
Public ContactCristina Varela
Pharma Clinical AG
Outcome results
None listed