PROactive Study

Study Description

PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events Study) is a landmark, 5,238–patient study looking at the potential for ACTOS® (pioglitazone HCl) to reduce the risk of death or recurrent macrovascular events (e.g. heart attack, stroke) in patients with type 2 diabetes who have already experienced a cardiovascular event– a very high–risk population.

Study Significance

Pioglitazone has been shown to improve specific lipid abnormalities commonly associated with type 2 diabetes. However, the clinical significance of these effects is still unknown. The PROactive study was designed to further evaluate the effects of pioglitazone on lipids and other markers of cardiovascular risk, and to determine if those effects translate into a reduction in cardiovascular mortality and morbidity in a high–risk population.
Cardiovascular disease is the leading cause of death for people with type 2 diabetes, who are two to four times more likely than people without type 2 diabetes to develop cardiovascular complications such as heart disease or stroke.

Study Design

PROactive is an ongoing randomized, double–blind, placebo–controlled outcome study, spanning 19 countries. The study enrolled 5,238 type 2 diabetes patients, who manage their diabetes with diet and/or oral blood glucose–lowering drugs, and who have a history of macrovascular disease.
Patients in the study are given pioglitazone as add–on therapy at the highest tolerated dose (up to 45 mg) or placebo, with other diabetes medications (non–TZD oral glucose–lowering agents with or without insulin) administered concomitantly.

Pioglitazone, an insulin sensitizer belonging to the thiazolidinedione (TZD) class of oral antidiabetic medications, acts primarily by decreasing insulin resistance.

Investigators were encouraged to maintain glycemia within the limit outlined in the International Diabetes Federation (IDF) Guidelines (A1C <6.5%). Investigators also were encouraged to optimize all therapy according to IDF Europe Guidelines by including lipid–lowering and antihypertensive therapy, as needed.
The aim of the study is to evaluate if pioglitazone has an effect on secondary prevention of macrovascular events in type 2 diabetes. The primary endpoint is the time from randomization to the first occurrence of any cardiovascular event in an individual patient. A statistically significant increase in time to cardiovascular event in the pioglitazone arm over the placebo arm would be considered a positive result.

Additional Information:

ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.

ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.

For prescribing information on pioglitazone, please visit the Web site ACTOS.com.