PIoglitazone for PrEvention of Restenosis in Diabetic Patients

NCT00376870 | Unknown Phase 3 DMC

• 1 other identifier: PIPER
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 2

Brief Summary

Restenosis requiring reintervention is still a limitation of percutaneous coronary angioplasty. Despite the use of Drug eluting stent (DES), the rate of restenosis remains 7% to 16% in diabetic patients, making it a challenging problem in interventional cardiology. Still, in clinical trials, most of these attempts did not successfully limit neointimal formation after coronary stenting. Thiazolidinediones (TZDs), like pioglitazone (pio) or rosiglitazone, are a novel class of oral antidiabetic agents currently used to treat patients with type 2 diabetes mellitus. These agents increase insulin sensitivity and, as such, have favorable effects on blood glucose levels and the lipid profile in treated patients. Beyond their metabolic action, TZDs have been shown to exhibit antiinflammatory and antiatherogenic effects in vascular cells in vitro and to limit lesion development in various animal models of arteriosclerosis. Moreover, TZDs inhibit VSMC proliferation and migration, 2 critical processes in neointimal formation after coronary stenting. Data from rodent models suggest that TZDs limit intimal proliferation after vascular injury, and in clinical studies with type 2 diabetic coronary artery disease (CAD) patients, TZDs have been shown to reduce neointimal formation as well as restenosis after coronary stent implantation. Still, it remains unclear to what extend these effects depend on the metabolic action of these drugs and what might mainly be due to the improvement in glycemic control. Recently a few reports on prevention of restenosis in type 2 diabetic patients (T2DM) with the use of TZDs as been published. All of them uses BMS as endoprosthetic devices. None of these evaluated the use of TZDs in combination with DES. Aim of the study is to evaluate the efficacy of pioglitazone in prevention of in-stent restenosis after successful implantation of a sirolimus-eluting coronary stent for treatment of de-novo "complex" coronary vessel disease in patients with T2DM and stable coronary artery disease. Study primary end-point are late-loss at 9 months.Secondary end-point include binary restenosis MACE at 1, 9 and 12 month, stent thrombosis at 12 months.

Conditions

Coronary Atherosclerosis; Coronary Restenosis; Diabetes

Keywords

PCI; STENT; Coronary; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• In-Segment Late Loss

  9 months

Secondary Outcomes (3)

• Binary restenosis

  9 months

• MACE

  1, 9, 12 month

• Stent thrombosis

  12 month

Study Arms (2)

Pioglitazone

ACTIVE COMPARATOR

Pioglitazone 30mg/d

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Pioglitazone DRUG

pioglitazone 30 mg/d

Pioglitazone

Placebo DRUG

Placebo 30 mg/d

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be previously diagnosed with type 2 diabetes with documented treatment with insulin, oral hypoglycemics, or diet controlled by medical history. (Undocumented or newly diagnosed diabetics must fulfill the American Diabetes Association Criteria-Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (Diabetes Care 2003;26:S5-20)).
• Diagnosis of angina pectoris defined by Canadian Cardiovascular Society Classification (CCS I, II, III, IV) OR unstable angina pectoris (Braunwald Classification B\&C, I-II-III) OR patients with documented silent ischemia;
• Patients with "de novo" coronary lesion (any length) who are eligible for coronary revascularization;
• Target lesion is ≥2.5 mm to ≤3.5mm in diameter (visual estimate);
• Target lesion stenosis is ≥50% (visual estimate);
• Male or Female age \>18 years old;
• Patients with one or more lesions to be treated with a sirolimus eluting stent (Cypher, Cordis);
• Patient must provide written informed consent prior to the procedure using a form that is approved by the local Institutional Review Board.
• At least one lesion must be a complex lesion (see below for details)

You may not qualify if:

• Patients under age 18 years old;
• Patient has experienced an ST-segment elevation myocardial infarction within the preceding 30 days;
• Active liver disease (ALT\>2.5 times upper limit of normal);
• Impaired renal function (creatinine ≥2.5 mg/dL);
• Previous brachytherapy of target vessel;
• Lesion of the Left Main trunk \> 50%;
• Target lesion is in a saphenous venous graft or internal mammary graft;
• Target lesion is due to restenosis ;
• Recipient of heart transplant;
• Women who are pregnant or who have the potential to become pregnant during the study;
• Patients with life expectancy of less than one year or factors making clinical follow-up difficult;
• Patients with bleeding diathesis in whom anticoagulant or antiplatelet drug is contraindicated;
• Patient with intolerance/contraindication to Aspirin or Ticlopidine/Clopidogrel or pioglitazone treatment;
• Currently participating in an investigational drug or another device study;
• Patients with leukopenia;

Sponsors & Collaborators

• University of Rome Tor Vergata: lead

Study Sites (2)

Policlinico di Tor Vergata

Rome, 00133, Italy

NOT YET RECRUITING

Policlinico di Tor Vergata

Rome, 00133, Italy

RECRUITING

Related Publications (1)

• Clementi F, Di Luozzo M, Mango R, Luciani G, Trivisonno A, Pizzuto F, Martuscelli E, Mehta JL, Romeo F. Regression and shift in composition of coronary atherosclerotic plaques by pioglitazone: insight from an intravascular ultrasound analysis. J Cardiovasc Med (Hagerstown). 2009 Mar;10(3):231-7. doi: 10.2459/JCM.0b013e3283212eb6.

  PMID: 19262209 DERIVED

Related Links

• University web page
• Hospital web page

MeSH Terms

Conditions

Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Coronary Stenosis; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Francesco Romeo, MD

  University of Rome Tor Vergata

  STUDY CHAIR

Central Study Contacts

Fabrizio Clementi, MD, PhD

CONTACT

+390620904009; fabrizio.clementi@me.com

Ruggiero Mango, MD

CONTACT

+393288982448; mango@med.uniroma2.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 13, 2006
• First Posted: September 15, 2006
• Study Start: July 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: April 1, 2011
• Last Updated: August 1, 2008

Record last verified: 2008-06

Locations

IT (2)