Efficacy Study of Pioglitazone and Atorvastatin Combination Therapy in Treating Subjects With Elevated Risk for Cardiovascular Disease
Condition: Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and
      atorvastatin combination therapy compared to atorvastatin monotherapy in patients at risk for
      cardiovascular disease.
    

Detailed description: 
      Carotid intima-media thickness is a well described surrogate marker for cardiovascular risk.
      A thickened carotid intima media layer correlates not only with the presence of
      cardiovascular risk factors but also the risk of future macrovascular events such as
      myocardial infarction and stroke. The interventional approach of cardiovascular risk factors
      with angiotensin converting enzyme system blockers, calcium antagonists or beta blockers can
      result in reduction of progression or even net regression of carotid intima-media thickness.
      The most potent agents, however, are statins which have consistently shown effects on carotid
      intima-media thickness in patients with hypercholesterolemia and/or atherosclerotic disease.

      Peroxisome proliferator activator receptor-gamma activation by thiazolidinediones is a
      promising new approach which reduces insulin resistance and improves lipid profile. In
      addition to their metabolic activities, peroxisome proliferator activator receptor-gamma
      activators were shown to exert anti-inflammatory effects, to improve endothelial function and
      to inhibit atherogenesis in diabetic and in non-diabetic atherosclerosis-prone animal models.
      Treatment with peroxisome proliferator activator receptor-gamma agonists have shown to reduce
      arterial pressure and carotid intima-media thickness in diabetic and non-diabetic patients at
      risk for cardiovascular disease.

      The aim of this study is to evaluate the effect of Pioglitazone in addition to Atorvastatin
      compared to Atorvastatin alone on vascular risk markers and intima-media thickness in
      patients with elevated risk for cardiovascular disease.
    

Intervention name(s): Pioglitazone and atorvastatin; Atorvastatin
Intervention type(s): Drug; Drug
Intervention description(s): Pioglitazone 30 mg, capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increase to:
Pioglitazone 45 mg, capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks.; Pioglitazone placebo-matching capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increased to
Pioglitazone placebo-matching capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks.
Other intervention name(s): ACTOS®; AD4833
Intervention MeSH terms: Pioglitazone; Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Biological Markers; Biochemical Markers; Carotid Artery, Internal; Carotid Artery, Common; Marker, Surrogate; Vascular Diseases; Diabetes Mellitus; Drug Therapy