Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 Diabetes (PROactive)
The purpose of this study is to determine whether pioglitazone, once daily (QD), can delay the time to death, heart attack, acute coronary syndrome, heart bypass surgery, stroke, leg bypass surgery or amputation in patients with type 2 diabetes.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study in Type 2 Diabetic Patients Comparing Pioglitazone With Placebo in Addition to Existing Therapy|
- Time to the Composite of All Cause Mortality, Non-Fatal Myocardial Infarction, Stroke, Acute Coronary Syndrome, Major Leg Amputation, Cardiac Intervention, Bypass Surgery or Leg Revascularization. [ Time Frame: At First Occurrence ] [ Designated as safety issue: Yes ]
- Time to All Cause Mortality. [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Non-Fatal Myocardial Infarction. [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Acute Coronary Syndrome. [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Cardiac Intervention (including coronary artery bypass graft or percutaneous coronary intervention). [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Stroke. [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Major Leg Amputation (above the ankle). [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Bypass Surgery [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Revascularization of the Leg. [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
- Time to Cardiovascular Mortality. [ Time Frame: At occurrence ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2001|
|Study Completion Date:||January 2005|
|Primary Completion Date:||January 2005 (Final data collection date for primary outcome measure)|
|Experimental: Pioglitazone QD||
Pioglitazone 15 mg to 45 mg, tablets, orally, once daily for up to 48 months.
|Placebo Comparator: Placebo QD||
Pioglitazone placebo-matching tablets, orally, once daily for up to 48 months
Diabetes mellitus is one of the most common non-communicable diseases worldwide. More than 22 million persons have been diagnosed with diabetes in the European region of the International Diabetes Federation. Complications of diabetes involving both microvascular and macrovascular systems contribute to increased disability and reduced life expectancy. Damage to the coronary, cerebral (brain), and peripheral vascular beds as a consequence of diabetes is responsible for the increased macrovascular illness and death associated with the disease.
Insulin resistance is common to the genesis of both atherosclerosis and type 2 diabetes mellitus. In diabetes, insulin resistance is coupled to receptor dysfunction. In atherosclerosis, insulin resistance may have both direct effects on the cardiovascular system as well as indirect effects provoked by imbalances in blood glucose, lipids, clotting factors, endothelial function, and other factors. Considerable indirect evidence suggests that peroxisome proliferator-activated receptor agonists may favorably influence macrovascular outcome, either through modification of risk factors (such as blood lipids) or through effects on the vessel wall.
Pioglitazone, a thiazolidinedione compound discovered by Takeda Pharmaceutical Company, Ltd, functions as a peroxisome proliferator-activated receptor agonist as its mode of action.
This study is designed to assess whether pioglitazone in combination with other medications administered for glycemic management of type 2 diabetes might reduce the incidence of macrovascular events associated with this disease compared with placebo. Individuals who participate in this study will provide written informed consent and will be required to commit to screening and randomization visits and approximately 17 additional visits (1 every 2 months for the first year and every 3 months thereafter) at the study center. Study participation is anticipated to be about 40 months (or approximately 3 years and 4 months). Multiple procedures will occur at each visit which may include fasting, blood collection, physical examinations and electrocardiograms.
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|Study Director:||European Development Director||Takeda|