Efficacy of Pioglitazone on Myocardial Function in Patients Undergoing Coronary Stent Implantation.

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00771004
First received: October 9, 2008
Last updated: July 1, 2010
Last verified: July 2010
  Purpose

The purpose of this study is to determine the effects of pioglitazone, once daily (QD), on heart functioning before, during and after stent implantation.


Condition Intervention Phase
Oxidative Stress
Coronary Artery Disease
Type 2 Diabetes
Drug: Pioglitazone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Trial Studying the Effects of Pioglitazone in Comparison to Placebo on Myocardial Function and Oxidative Stress in Patients With Type II Diabetes and Insulin Resistance Undergoing Elective PTCA. A Randomized Double-blinded Phase II Study.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Incidence of Cardiac Troponin I elevation (greater than 1 upper limit of normal) post-percutaneous coronary intervention with stent implantation. [ Time Frame: 24 hours post stent implantation. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of Creatine Kinase (Myocard-type) post-percutaneous coronary intervention with stent implantation. [ Time Frame: 24 hours post stent implantation. ] [ Designated as safety issue: No ]
  • Mean peak values of Troponin I and Creatine Kinase (Myocard-type) post-percutaneous coronary intervention with stent implantation. [ Time Frame: Hours: 2, 6 and 12 and 24 post stent implantation. ] [ Designated as safety issue: No ]
  • Frequency of Doppler-detected microembolism measured by high intensity transient signals during percutaneous coronary intervention with stent implantation (sub-study Jena only). [ Time Frame: Duration of stent implantation surgery. ] [ Designated as safety issue: No ]
  • Time course of Troponin I Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of high-sensitive-C-Reactive Peptide Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of nitrotyrosine Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of Asymmetric dimethylarginine Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of E-selectin Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of Myoglobin Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of Visfatin Laboratory Procedure. [ Time Frame: Visits: 2, 3, 4, 5, 6, 7, and 8 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of Proinsulin intact Laboratory Procedure. [ Time Frame: Visits: 1 and 7 or Final Visit. ] [ Designated as safety issue: No ]
  • Time course of Adiponectin Laboratory Procedure. [ Time Frame: Visits: 1 and 7 or Final Visit. ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: August 2006
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone 30 mg to 45 mg QD Drug: Pioglitazone
Pioglitazone 30 mg, tablets, orally, once daily for one week; increased to Pioglitazone 45 mg, tablets, orally, once daily for up to two weeks.
Other Names:
  • ACTOS®
  • AD4833
Placebo Comparator: Placebo QD Drug: Placebo
Pioglitazone placebo-matching tablets, orally, once daily for up to three weeks.

Detailed Description:

Type 2 diabetes increases the risk of coronary heart disease at least by two to three fold compared with non-diabetic subjects. Moreover, prospective studies have shown a significant correlation between several glycemic confounders and morbidity from coronary heart disease even in patients without diabetes mellitus. In patients with previously diagnosed coronary heart disease, impaired glucose tolerance was found in 30 to 67 %. The cardiovascular risk of patients with insulin resistance, with or without glucose intolerance has become more and more apparent within recent years and quantitative coronary angiographic studies have revealed a correlation between the severity of coronary heart disease and impaired glucose tolerance.

A new pharmaceutical class for the intervention of insulin resistance, the peroxisome proliferator activated receptor (gamma) agonists have been successfully introduced in the treatment of type 2 diabetes. Beyond their metabolic effects on glucose and lipid metabolism, peroxisome proliferator activated receptor (gamma) agonists show to exert a couple of pleiotropic, anti-inflammatory and vasoprotective effects in patients with type 2 diabetes and impaired glucose tolerance.

The incidence and severity of peri-procedural myocardial injury during percutaneous coronary interventions with stent implantation in diabetic and in non-diabetic patients is an important prognostic confounder for the patient. Different laboratory biomarkers have been investigated as diagnostic tools for the estimation of the risk of peri-procedural myocardial injury. Recent studies have convincingly demonstrated that the risk of subsequent ischemic heart events is related to the extent of cardiac troponin or CK-MB increase after coronary intervention, and the prognosis for these individuals is usually worse than that for patients who do not develop an increase in these biomarkers.

In a recent trial it was shown that pretreatment with atorvastatin could reduce procedural myocardial injury in elective coronary intervention. The incidence of Troponin I increase was 48% in the placebo group compared to 20% in the atorvastatin group.

The aim of this study is to investigate the effect of pioglitazone on the incidence of peri-procedural myocardial injury in patients undergoing percutaneous coronary interventions with stent implantation. Total participation time is anticipated to be 3 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stable coronary artery disease with planned percutaneous coronary intervention with stent implantation.
  • Type II-diabetics and/or an IRIS II score greater than or equal to 50 (measure for the identification of patients with insulin resistance and increased vascular risk).
  • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria:

  • A planned percutaneous coronary intervention with stent implantation less than 15 days after the screening visit.
  • Planned multi-vessel intervention.
  • Use of systemic corticosteroids within the last 3 months prior to screening visit.
  • Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
  • History of severe or multiple allergies.
  • Treatment with any other investigational drug within 3 months before trial entry or earlier participation in the present study.
  • Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit.
  • Progressive fatal disease.
  • History of drug or alcohol abuse within the last 10 years.
  • A history of significant cardiovascular (New York Health Association stage II - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase greater than 2.5 times the normal reference range), renal (creatinine greater than 1.2 mg/dL in women and greater than 1.5 in men and/or glomerular filtration rate less than 45), neurological, psychiatric and/or hematological disease as judged by the Investigator.
  • Pre-treatment with peroxisome proliferator-activated receptor (gamma) agonists within the 3 months prior to screening.
  • If insulin therapy applicable: initiation of insulin therapy within the last 3 months.
  • If statin therapy applicable: change of medication within the last 4 weeks.
  • Myocardial infarction within 3 months prior to screening visit.
  • Blood donation within last 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00771004

Locations
Germany
Frankfurt, Hessen, Germany
Kassel, Hessen, Germany
Wiesbaden, Hessen, Germany
Wuppertal, Nordrhein-Westfalen, Germany
Mainz, Rheinland-Pfalz, Germany
Jena, Thüringen, Germany
Hamburg, Germany
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Adviser Clinical Research Takeda Pharma Gmbh, Aachen (Germany)
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Director, Takeda Pharma GmbH, Aachen (Germany)
ClinicalTrials.gov Identifier: NCT00771004     History of Changes
Other Study ID Numbers: ATS K021, 2006-002237-20, D-PIO-111, U1111-1115-9160
Study First Received: October 9, 2008
Last Updated: July 1, 2010
Health Authority: European Union: European Medicines Agency

Keywords provided by Takeda:
drug effects
Type II Diabetes
Angioplasty, Transluminal, Percutaneous Coronary
Drug Therapy
Heart
physiology
function

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014