Efficacy Study of Pioglitazone and Atorvastatin Combination Therapy in Treating Subjects With Elevated Risk for Cardiovascular Disease
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|ClinicalTrials.gov Identifier: NCT00770575|
Recruitment Status : Completed
First Posted : October 10, 2008
Last Update Posted : July 5, 2010
|Condition or disease||Intervention/treatment||Phase|
|Cardiovascular Diseases||Drug: Pioglitazone and atorvastatin Drug: Atorvastatin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||148 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Double Blinded Study of the Effects of Pioglitazone in Combination With Atorvastatin in Comparison to Atorvastatin Treatment Alone on Intima-Media Thickness in Patients at Risk for Vascular Complications|
|Study Start Date :||June 2005|
|Actual Primary Completion Date :||October 2006|
|Actual Study Completion Date :||October 2006|
|Experimental: Pioglitazone 30mg to 45 mg QD + Atorvastatin 20 mg to 40 mg QD||
Drug: Pioglitazone and atorvastatin
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.
|Active Comparator: Atorvastatin 20mg to 40 mg QD||
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.
- Change in the intima-media thickness of the common carotid artery. [ Time Frame: Week 24. ]
- Change in the intima-media thickness of the internal carotid artery. [ Time Frame: Week 24. ]
- Change in the intima-media thickness of the carotid bulbus. [ Time Frame: Week 24. ]
- Change from Baseline in Efficacy Laboratory findings (Interleukin-6, high sensitive C reactive peptide and monocyte chemotactic protein-1) [ Time Frame: Week: 24. ]
- Change from Baseline in Efficacy Laboratory findings (matrix metalloproteinase-9, soluble CD40 Ligand, P-Selectin, soluble intracellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1). [ Time Frame: Week: 24. ]
- Change from Baseline in Efficacy Laboratory findings (adiponectin, tissue plasminogen activator, Plasma glucose, Insulin and Intact proinsulin). [ Time Frame: Week: 24. ]
- Change from Baseline in Efficacy Laboratory findings (blood lipids (total cholesterol, high density lipoprotein, triglycerides) and low density lipoprotein-subfractions). [ Time Frame: Week: 24. ]
- Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Week: 24. ]
- Change from Baseline in Beta cell function (Homeostatic Model Assessment - beta cell response Score). [ Time Frame: Week: 24. ]
- Change from Baseline in Insulin sensitivity using the Homeostatic Model Assessment - Sensitivity Score). [ Time Frame: Week: 24. ]
- Change from Baseline in Microcirculation assessment. [ Time Frame: Week: 24. ]
- Change from Baseline in Pulse wave velocity. [ Time Frame: Weeks: 12 and 24. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00770575
|Study Director:||Head of Clinical Research/Licensing/New Products||Takeda Pharma Gmbh, Aachen (Germany)|