PIoglitazone for PrEvention of Restenosis in Diabetic Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by University of Rome Tor Vergata.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Rome Tor Vergata
ClinicalTrials.gov Identifier:
NCT00376870
First received: September 13, 2006
Last updated: July 30, 2008
Last verified: June 2008
  Purpose

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.


Condition Intervention Phase
Coronary Atherosclerosis
Coronary Restenosis
Diabetes
Drug: Pioglitazone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prevention of Coronary Artery in STENT Restenosis With the Combined Use of Pioglitazone and Sirolimus-Eluting Coronary Stent

Resource links provided by NLM:


Further study details as provided by University of Rome Tor Vergata:

Primary Outcome Measures:
  • In-Segment Late Loss [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Binary restenosis [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  • MACE [ Time Frame: 1, 9, 12 month ] [ Designated as safety issue: Yes ]
  • Stent thrombosis [ Time Frame: 12 month ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 160
Study Start Date: July 2008
Estimated Study Completion Date: April 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pioglitazone
Pioglitazone 30mg/d
Drug: Pioglitazone
pioglitazone 30 mg/d
Placebo Comparator: Placebo Drug: Placebo
Placebo 30 mg/d

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

I5.1 Inclusion criteria

  • 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)

5.2 Exclusion criteria

  • 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;
  • Patients with neutropenia;
  • Documented peptic ulcer or gastric/intestinal bleeding in the last 6 months;
  • Patients with thrombocytopenia.
  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: NCT00376870

Contacts
Contact: Fabrizio Clementi, MD, PhD +390620904009 fabrizio.clementi@me.com
Contact: Ruggiero Mango, MD +393288982448 mango@med.uniroma2.it

Locations
Italy
Policlinico di Tor Vergata Not yet recruiting
Rome, Italy, 00133
Principal Investigator: Fabrizio Clementi, MD. PhD         
Policlinico di Tor Vergata Recruiting
Rome, Italy, 00133
Contact: Saverio Muscoli, MD    +390620904009    fabrizio.clementi@me.com   
Principal Investigator: Fabrizio Clementi, MD, PhD         
Sponsors and Collaborators
University of Rome Tor Vergata
Investigators
Study Chair: Francesco Romeo, MD University of Rome Tor Vergata
  More Information

Additional Information:
No publications provided by University of Rome Tor Vergata

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fabrizio Clementi
ClinicalTrials.gov Identifier: NCT00376870     History of Changes
Other Study ID Numbers: PIPER
Study First Received: September 13, 2006
Last Updated: July 30, 2008
Health Authority: Italy: Ministry of Health

Keywords provided by University of Rome Tor Vergata:
PCI
STENT
Coronary
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Coronary Artery Disease
Myocardial Ischemia
Coronary Restenosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Coronary Stenosis
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014