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.
Among patients throughout the world who experience a transient ischemic attack (TIA)or ischemic stroke, subsequent stroke and heart attack are major causes of death and disability. Within 4 years of the initial TIA or ischemic stroke, 16 percent of patients will have a recurrent stroke and 9 percent will have a heart attack. Prevention of further vascular events, therefore, is critically important to the health of patients with stroke.
The IRIS trial will test a new treatment strategy based on evidence linking insulin resistance to increased risk for stroke and other vascular diseases. Insulin resistance is a condition in which insulin, a normal human hormone, does not work effectively because the body is resistant to its effects. This condition can lead to diabetes and is thought to cause blood vessel disease, including stroke and heart attack, in patients with and without diabetes.
Insulin resistance affects up to 50% of stroke patients and is effectively modified with thiazolidinedione drugs (called "TZDs") used to treat type 2 diabetes. In addition to reducing insulin resistance, these drugs have other favorable effects on blood vessels, reduce blood vessel inflammation, and potentially prevent atherosclerosis. Currently marketed TZDs include rosiglitazone and pioglitazone.
The IRIS is a clinical trial that will enroll 3936 subjects at approximately 170 hospitals in Australia, Canada, Germany, Israel, Italy, the UK and the US. After an initial screening blood test, each participant will be randomly assigned to take either pioglitazone or placebo tablets. Recruitment will be completed during 2005-2012, and all participants will be followed for a minimum of 3 years.
- Pioglitazone (Pioglitazone)Drug
Intervention Desc: a thiazolidinedione drug ARM 1: Kind: Experimental Label: 1 Description: pioglitazone
- Placebo Drug
Intervention Desc: an inactive substance ARM 1: Kind: Experimental Label: 2
- Allocation: Randomized
- Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Efficacy Study
- Intervention: Parallel Assignment
Patients will be randomized to receive either 15 mg tablets of pioglitazone or placebo. The medication will be increased each month to a final dose of 3 pills daily. Thereafter, participants will receive tablets containing placebo or 45 mg pioglitazone once daily. After dose escalation, participants will be followed with scheduled telephone calls and annual in-person visits. Blood is drawn at 4 months and annually for safety and efficacy measures.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Cumulative total of fatal and non-fatal strokes and myocardial infarctions.|
|Secondary||Time to stroke alone; progression of diabetes; all cause mortality; cognitive decline.|
|Primary||Time to occurrence of recurrent fatal or non-fatal stroke, or fatal or non-fatal myocardial infarction||3 years||No|
|Secondary||1.time to stroke alone; 2.Diabetes Mellitus; 3.All Cause Mortality; 4.Cognitive Decline (change in score over time for the Modified Mini Mental State Examination)||3 years||No|
|Secondary||stroke, MI, or congestive heart failure||3 years||Yes|
|Secondary||time to fatal or non-fatal stroke alone||5 years||No|
|Secondary||time to acute coronary syndrome (fatal or non-fatal acute MI or unstable angina)||5 years||No|
|Secondary||Time to overt diabetes||5 years||No|
|Secondary||Time to all cause mortality||5 years||No|
|Secondary||Risk for decline in cognitive status||5 years||No|
|Secondary||Time to fatal or non-fatal stroke, fatal or non-fatal MI or episode of congestive heart failure||5 years||Yes|