PROspective PioglitAzone Clinical Trial in MacroVascular Events (PROactive)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Clinical trial
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Primary data collection

Clinical trials

• Clinical trial randomisation:
  Randomised clinical trial

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  PIOGLITAZONE HYDROCHLORIDE
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Short description of the study population:
  Patients aged 35-75 years old diagnosed with type 2 diabetes mellitus received pioglitazone with current diabetic treatment.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with type 2 diabetes mellitus
• Estimated number of subjects:
  5238

Study design details

• Main study objective:
  This study demonstrated that whether pioglitazone reduces total mortality and macrovascular morbidity in high-risk patients with type 2 diabetes mellitus.
• Outcomes:
  Time from randomization to first occurrence of any of the events in the following composite: all-cause mortality, non-fatal MI (including silent MI), acute coronary syndrome, cardiac intervention including CABG or PCI, stroke, major leg amputation, and bypass surgery or revascularization in the leg., Secondary outcomes included: composite of all-cause mortality, non-fatal MI (excluding silent MI), and stroke; Cardiovascular mortality; individual components of the primary endpoint.
• Data analysis plan:
  For each endpoint, treatment-group differences were examined using a log rank test without covariates; a Cox proportional hazards model was fitted with treatment as the only independent variable for estimate of the hazard ratio (95% confidence interval); Kaplan-Meier estimates of the survival functions were used to characterize treatment effects. Exploratory analyses were conducted using the proportional hazards model and incorporating additional covariates. 2 interim analyses were planned and conducted. The first was performed when approximately 50% of the anticipated final number of events had occurred and the second when approximately 75% of the events had occurred. These analyses were conducted by the Independent Statistical Centre and then reported to the Data and Safety Monitoring Committee. Each interim analysis for efficacy considered the 1-sided log rank test for the superiority of pioglitazone.