Insulin Resistance Intervention After Stroke Trial "IRIS"

Completed

Phase 3 Results

Trial Description

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.

Detailed Description

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.

Conditions

Interventions

  • 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

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

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.

Outcomes

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

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