Prevention of Instent Renarrowing With Aggressive Glucose Lowering With Pioglitazone in Diabetic Patients (PPAR-G)
|ClinicalTrials.gov Identifier: NCT00819325|
Recruitment Status : Completed
First Posted : January 8, 2009
Last Update Posted : January 8, 2009
Patients with diabetes have worse outcomes after percutaneous coronary intervention (PCI) procedures, compared to those patients without diabetes. They are at increased risk of death, heart attack, or needing further procedures due to renarrowing of their coronary narrowings after implantation of a coronary stent. Studies have suggested that poor control of diabetes may be partly responsible for these poor outcomes. Thiazolidinedione drugs, such as pioglitazone, can improve the diabetes control and make the patient more sensitive to the effects of insulin. Preliminary studies suggest that pioglitazone may also help prevent renarrowing after PCI.
This study was a pilot study designed to determine whether more aggressive treatment of the diabetes with the routine use of the drug pioglitazone (30mg/day for 6 months), in addition to the patient's usual diabetic medications adjusted to optimize their diabetic control (get glycated hemoglobin < 7%), could reduce the amount of tissue buildup within the stent after 6 months, compared to a group less aggressively treated without pioglitazone and their usual medications for diabetes.
An intravascular ultrasound probe was used to assess the extent of tissue buildup within the stent and this was performed immediately after the PCI as a baseline and repeated after 6 months of therapy.
The investigators hypothesize that the more aggressive diabetic treatment with pioglitazone would reduce the extent of tissue growth within the stent after 6 months of therapy.
|Condition or disease||Intervention/treatment||Phase|
|Coronary Artery Disease Angina Pectoris Type 2 Diabetes Mellitus Percutaneous Coronary Intervention||Drug: pioglitazone Drug: oral hypoglycemic agents||Phase 4|
Background: Despite drug-eluting stents (DES), diabetic patients remain at high risk of restenosis and poor clinical outcomes after percutaneous coronary intervention (PCI). Studies have suggested poor glycemic control and insulin resistance may be predictors of poor outcomes after PCI. There are conflicting studies as to whether strategies to improve glycemic control can improve outcomes after PCI. Thiazolidinediones, such as pioglitazone (PIO), may have anti-restenotic benefits, independent of glycemic control.
Study design: This study was a single centre prospective, randomized, open-label, blinded-endpoint (PROBE) parallel design trial. Type 2 diabetic patients, treated with diet or oral antidiabetic medication (sulfonylurea vs. metformin or combination; but no thiazolidinedione or insulin), who are undergoing elective or urgent PCI with stenting were eligible. Fifty type 2 diabetic patients were randomly assigned to either: intensive glycemic control: pioglitazone (PIO; 30 mg/d x 6 months) in addition to titration of oral hypoglycemic agents (OHA) to get HbA1c<6% (PIO: n=25) vs. conservative glycemic control: titration of OHA to get HbA1c<7% (CONTROL: n=25). Intravascular ultrasound (IVUS) was performed immediately after PCI and repeated at 6 months to determine the effect on instent neointimal plaque volume and area. Coronary stenting was carried out in a standard fashion, with routine use of a glycoprotein 2b/3a inhibitor during the procedure. From August 2002 until June 2005, DES were not permitted in the protocol. After June 2005, we amended the protocol to allow DES, as they had become routinely used in diabetic patients in our institution, especially for vessel size <3mm and/or lesion length>15mm. DES were used in 7 PIO and 11 CONTROL subjects, and bare metal stents (BMS) in the rest. Patients were then followed with clinic visits at 1, 3 and 6 months. OHA, other than pioglitazone, were adjusted in a stepwise manner in order to attain the HbA1c targets. Other concomitant medications, including anti-anginals, lipid-lowering therapy, and antihypertensive medication were adjusted according to their clinical need and current Canadian guidelines. After 6 months treatment, or before if clinically indicated, all subjects were to return for repeat cardiac catheterization, including repeat coronary angiography and IVUS of the intervened vessel to assess the serial change in luminal dimensions. Fasting blood was collected for plasma glucose, HbA1c, insulin, lipid profile, hs-CRP, adiponectin, leptin, matrix metalloproteinase-9, and interleukin-6 at the time of PCI and at the follow-up IVUS. If the patient developed recurrent ischemic symptoms before 6 months, the final IVUS could be performed earlier, if they were found to have clinically-significant restenosis (diameter stenosis > 50%). Otherwise, patients were still encouraged to have their protocol 6 month IVUS follow-up. 41 patients (n=20 PIO, n=21 CONTROL) had analyzable pairs of IVUS.
Study hypothesis: We hypothesized that there would be significantly less instent neointimal proliferation on IVUS at 6 months in the group receiving aggressive glycemic control plus the thiazolidinedione pioglitazone. We also hypothesized that the reduction in neointimal hyperplasia will likely relate to improvements in glycemic control (HbA1c) and insulin resistance. Additionally, we wanted to explore the biochemical predictors (glucose parameters, lipids, inflammatory markers, adipokines) for neointimal proliferation.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Prevention of Neointimal Proliferation With Aggressive Reduction of Glucose Concentrations (Pioglitazone) Study -- PPAR-G -- An IVUS Pilot Feasibility Study in Type 2 Diabetic Patients.|
|Study Start Date :||August 2002|
|Primary Completion Date :||November 2006|
|Study Completion Date :||March 2007|
Experimental: Intensive glycemic control
Included routine use of pioglitazone (30 mg/d) for 6 months in addition to titration of their other oral hypoglycemic agents in order to get the HbA1c<6%.
pioglitazone 30mg p.o. once a day for 6 monthsDrug: oral hypoglycemic agents
sulfonylurea or metformin
Active Comparator: conservative glycemic control
Included titration of oral hypoglycemic agents to get HbA1c<7% without the use of a thiazolidinedione.
Drug: oral hypoglycemic agents
sulfonylurea or metformin
- The primary IVUS endpoint of the study was the change in three-dimensional neointimal plaque volume within the stented segment at follow-up, compared to baseline. [ Time Frame: 6 months ]
- The secondary IVUS endpoint was the change in the two-dimensional NIA within the stent, using the cross-sectional slice showing the smallest LA on follow-up and comparing it to the corresponding baseline slice. [ Time Frame: 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00819325
|Canada, Nova Scotia|
|Queen Elizabeth II Health Sciences Centre|
|Halifax, Nova Scotia, Canada, B3H 3A7|
|Principal Investigator:||Lawrence M Title, MD FRCPC||QE II Health Sciences Centre|