Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 Diabetes

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00174993
• Date of registration: 09/09/2005
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 Diabetes PROactive
• Scientific 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
• Date of first enrolment: May 2001
• Target sample size: 4373
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00174993
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Slovakia, Sweden, Switzerland, United Kingdom

Contacts

• Name: European Development Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria

- Type 2 diabetes mellitus

- Glycosylated hemoglobin above the upper limit of normal (ie, the local equivalent of
6.5% for)

- Established history of macrovascular disease, defined as 1 or more of:

- Myocardial infarction at least 6 months before entry into the study.

- Stroke at least 6 months before entry into the study

- Percutaneous coronary intervention or coronary artery bypass graft at least 6
months before entry into the study.

- Acute coronary syndrome at least 3 months before entry into the study.

- Objective evidence of coronary artery disease.

- Peripheral arterial obstructive disease

Exclusion Criteria

- Signs of type 1 diabetes.

- Patients prescribed insulin as sole therapy for glycemic control of diabetes for 2
weeks or more at any time in the previous 3 months.

- Myocardial infarction, stroke, coronary artery bypass graft, or percutaneous cardiac
intervention in the 6 months prior to enrolment.

- Acute coronary syndrome in the 3 months prior to enrolment.

- Heart failure at entry defined as patient having a New York Heart Association
functional score of II or above.

- Had an appointment for a coronary angiogram or endovascular or surgical intervention.

- Leg ulcers, gangrene, or ischemic rest pain.

- Had an appointment for an angiogram or endovascular or surgical intervention for leg
ischemia.

- Had undergone a major operation (defined as a surgical procedure lasting for more
than 30 minutes) at any time in the previous 4 weeks.

- Significantly impaired hepatic function, defined as alanine aminotransferase greater
than 2.5 times the upper limit of normal.

- Familial polyposis coli.

- Required dialysis.

- History of alcohol or drug abuse.

- Any other intercurrent disease believed to be likely to have a significant impact on
the patient's life expectancy during the course of the study (eg, cancer).

- Patient was undergoing follow-up as part of another clinical trial or less than 3
months had elapsed since the last dose of an investigational drug or procedure.

- Hypersensitivity to pioglitazone or other TZD.

- Current use of pioglitazone or other TZD.

- Patient was known to be infected with human immunodeficiency virus or was known to
have viral hepatitis.

- Women who were any of the following: pregnant, breast feeding, wished to become
pregnant during the course of the study or of childbearing potential and not planning
to use a reliable method of contraception throughout the study.



Age minimum: 35 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Diabetes Mellitus

Intervention(s)

Drug: Placebo

Drug: Pioglitazone

Primary Outcome(s)

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]

Secondary Outcome(s)

Time to Cardiac Intervention (including coronary artery bypass graft or percutaneous coronary intervention). [Time Frame: At occurrence]

Time to All Cause Mortality. [Time Frame: At occurrence]

Time to Revascularization of the Leg. [Time Frame: At occurrence]

Time to Bypass Surgery [Time Frame: At occurrence]

Time to Major Leg Amputation (above the ankle). [Time Frame: At occurrence]

Time to Cardiovascular Mortality. [Time Frame: At occurrence]

Time to Stroke. [Time Frame: At occurrence]

Time to Acute Coronary Syndrome. [Time Frame: At occurrence]

Time to Non-Fatal Myocardial Infarction. [Time Frame: At occurrence]

Secondary ID(s)

U1111-1114-2854

AD4833/EC444

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eli Lilly and Company