PROactive investigates effect of ACTOS® (pioglitazone HCl) on cardiovascular disease progression

06/25/04

More than 5,000 patients with type 2 diabetes studied

Lincolnshire, IL, June 28, 2004 – In the July 2004 issue of Diabetes Care, researchers published the study design and baseline characteristics of patients enrolled in the landmark PROspective PioglitAzone Clinical Trial In MacroVascular Events Study (PROactive). PROactive is a European clinical trial assessing the effects of ACTOS® (pioglitazone HCl) on mortality and morbidity associated with cardiovascular disease progression in patients with type 2 diabetes. The study has enrolled 5,238 patients in 19 countries who have experienced one or more cardiovascular events such as a heart attack, coronary artery bypass surgery or stroke.

"Major studies have shown that sustained improvements in glycemic control significantly reduce the risk of some microvascular complications, but data remain inconclusive that intervention with conventional glucose-lowering agents is successful in modifying macrovascular disease," said John Dormandy, M.D., professor of Vascular Sciences at St. George's Hospital, London, and chairman of the PROactive study steering committee. "Recent studies have shown ACTOS has a beneficial effect on markers of cardiovascular risk, such as atherogenic lipids and c-reactive protein (CRP). Through PROactive, we will determine if the beneficial effects of ACTOS on cardiovascular risk factors translate into a reduction in cardiovascular mortality and morbidity in a high-risk population of patients with type 2 diabetes."

Type 2 diabetes is associated with a two- to four-fold increase in cardiovascular disease as well as other cardiovascular risk factors such as high blood pressure and cholesterol disorders. Additionally, heart disease is the leading cause of mortality and morbidity for patients with type 2 diabetes.

"Previous studies have suggested ACTOS can provide benefits extending beyond improvements in glucose levels," said John Yates, M.D., M.R.C.P., president, Takeda Global Research & Development. "Physicians who treat patients with type 2 diabetes face increasing challenges helping their patients manage cardiovascular risk factors. PROactive should generate important insights into whether the drug can play a larger role in the management of this devastating disease."

In several large-scale trials, ACTOS consistently improved components of diabetic dyslipidemia, another cardiovascular disease risk factor, which is characterized by low HDL ("good") cholesterol levels and high triglycerides. Smaller, mechanistic studies have shown statistically significant changes in small, dense LDL cholesterol and in CRP, an important marker of inflammation and a key factor in the development of coronary artery disease.

Study Design

PROactive is an ongoing randomized, double-blind, placebo-controlled outcome study assessing the incidence of cardiovascular complications of diabetes, e.g., heart attack, coronary artery bypass surgery or stroke, as well as overall mortality. The primary endpoint variable is the time from randomization to the first occurrence of any of the events in the composite endpoint, including death and major macrovascular events.

Pioglitazone or placebo is given as add-on therapy to existing diabetes management (including diet and exercise and other diabetes medications). Study medication was assigned using a central interactive voice response system. Investigators are encouraged to maintain glycemia within the limits outlined in the International Diabetes Federation (IDF) Europe Guidelines (A1C<6.5%).

Patients in the study are given pioglitazone 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. Investigators optimize all therapy according to IDF Europe Guidelines by providing lipid-lowering and antihypertensive therapy, as needed. Patients who discontinue the study medication are being followed until the end of the study, with the study completion expected in 2005.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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