Ignite Creation Date:
2024-05-05 @ 5:13 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00412126
Status:
COMPLETED
Last Update Posted:
2006-12-15
First Post:
2006-12-13
Brief Title:
Clinical and Angiographic Outcomes With Hyperglycemic Control Post PCI
Sponsor:
Hamilton Health Sciences Corporation
Organization:
McMaster University
Study Overview
Official Title:
Does Reduction of Hyperglycemia With Insulin Impact Restenosis and Improve Clinical Outcomes Following PCI
Status:
COMPLETED
Status Verified Date:
2006-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Coronary artery disease is a process that results in hardening of the arteries When the arteries that supply blood and oxygen to your heart muscle become clogged or narrowed a heart attack may result or you may feel chest discomfort angina - sometimes even while resting One approach to treating this condition is a balloon procedure known as coronary angioplasty
The major limitation of coronary angioplasty is renarrowing of the artery restenosis in the first six months following the procedure requiring either repeat angioplasty or referral for bypass surgery Patients with diabetes have always been identified as having higher rates of restenosis and poor outcomes following angioplasty despite some important scientific advances We think that the level of blood sugar control at the time of angioplasty and in the following months may be related to the extent of restenosis
We expect that a reduction in blood sugar with insulin may in turn reduce the restenosis process and improve your long-term outcome
The major limitation of coronary angioplasty is renarrowing of the artery restenosis in the first six months following the procedure requiring either repeat angioplasty or referral for bypass surgery Patients with diabetes have always been identified as having higher rates of restenosis and poor outcomes following angioplasty despite some important scientific advances We think that the level of blood sugar control at the time of angioplasty and in the following months may be related to the extent of restenosis
We expect that a reduction in blood sugar with insulin may in turn reduce the restenosis process and improve your long-term outcome
Detailed Description:
Studies consistently show that diabetes DM is an independent predictor of angiographic restenosis as well as clinical outcomes after PCI A common criticism of the early PCI trials is that stents were not routinely used However even when stents are used the presence of DM is associated with a higher restenosis rate and lower event rate survival In a series of 3554 consecutive patients 715 DM patients undergoing stenting procedures at a single centre the incidence of restenosis and total vessel occlusion by angiographic assessment was significantly higher in diabetes Increased restenosis rates were consistently demonstrated across a broad range of lesion types
The pathophysiology of restenosis is viewed as a complex temporal sequence of interactions involving several cellular and mechanical factors including elastic recoil thrombosis intimal hyperplasia extra cellular matrix elaboration apoptosis oxidative stress and unfavorable arterial remodeling arterial shrinkage The exposure of subendothelial elements initiates platelet adhesion and activation Activated platelets at the site of injury secrete growth factors that release smooth muscle cells from growth inhibition and induce their proliferation and subsequent migration from the media to the intima Smooth muscle cell proliferation continues beyond the phase of platelet deposition Extracellular matrix is produced and secreted by smooth muscle cells that have migrated into the injured intimal zone This hypocellular matrix material forms the bulk of the intimal tissue Although mechanical factors such as early vessel elastic recoil may play a major role following balloon angioplasty this mechanism should not significantly affect the stented segments as the stent provides a rigid endovascular scaffold Similarly late arterial remodelling which has been postulated to be a significant factor for the development of restenosis after PCI should not have a major effect in the context of stents Therefore the major mechanism contributing to in-stent restenosis is aggressive intimal hyperplasia
Recent studies demonstrate that DM is characterized by diffuse intimal hyperplasia within the stented segment DM is an independent predictor of the volume of intimal hyperplasia within the stent The pattern of stent restenosis in patients with DM tends to be more diffuse and proliferative and therefore more likely to lead to total vessel occlusion This is significant because diffuse restenosis is difficult to manage with repeat percutaneous procedures
Hyperglycemia has been postulated to promote the restenotic process in diabetes by the following mechanisms i endothelial cell dysfunction ii increased platelet aggregation and thrombus formation iii dysregulation of growth factor expression iv abnormal extracellular matrix deposition v advanced isolation and products
Approaches to preventing stent restenosis have had limited effect Pharmacologic trials have universally failed to show a reduction in restenosis rates in human subjects Recent reports suggested radiation therapy brachytherapy especially applied locally either via catheters or through radioactive stents has a potential to reduce the proliferative response Although this approach holds great promise there are unresolved logistic issues safety issues and cost issues limiting wide-spread application
Preliminary studies of drug-eluting stents show initial promise in reducing restenosis rates However stent coatings can counteract the restenotic process only at points where the stent strut opposes the arterial wall and have little effect on neointimal tissue that can protrude between the struts and into the lumen Furthermore both brachytherapy and stent coatings only apply to the stented segments and the vessel whereas the arterial responses to balloon injury may also depend on flow characteristics ie rheology of the vessel Therefore alternative strategies that impact both local processes of the dilatation site and systematic processes on vessel remodelling and rheology are needed
Clinical trial data suggests that glycemic control may prevent restenosis A recent study of patients with type 2 diabetes undergoing PCI with stent demonstrated a significant reduction in both neointimal area and neointimal index among participants randomized to the glucose-lowering agent troglitazone Observational data from two registry studies indicate that diabetic patients with well-controlled hemoglobin A1c had lower rates of restenosis
Several lines of evidence suggest that insulin is safe and effective in controlling diabetes as well as reducing cardiovascular events The recently published DIGAMI Study in which patients with myocardial infarction were randomized to an insulin infusion followed by at least three months of intensified insulin therapy showed a 31 reduction mortality in patients receiving intensified therapy Subcutaneous insulin has been safely used to treat diabetes for almost 80 years Patients can easily learn to both inject and titrate insulin response to home capillary glucose measurements Greater than 85 of patients with type II diabetes who were started on insulin can achieve safe and effective metabolic control with one injection per day
Intravascular ultrasound is the most direct and sensitive technology available for measurement of intravascular hyperplasia volume within the stent It is the technology that is most likely to uncover a benefit of insulin in reducing restenosis if one exists This methodology will allow the research question to be answered with the smallest possible sample size Recent studies demonstrate that detailed cross-sectional analysis of intracoronary stents during motorized IVUS catheter pullback is feasible with excellent reproducibility safety and can be stored for off-line analysis Establishing a mechanistic link between glycemic control and restenosis will support the design of larger clinical studies evaluating clinical outcomes
Primary Study Question
Does intensive control of glucose levels with insulin in patients with DM reduce volume of intimal hyperplasia within the stented segment as evaluated by intravascular ultrasound IVUS at 6 months Secondary Study Question
Does intensive glycemic control with insulin reduce restenosis as evaluated by quantitative coronary angiography QCA at 6 months
Does intensive glycemic control with insulin prevent clinical events such as hospital admission for unstable angina and for congestive heart failure myocardial infarction stroke revascularization PCI CABG and death at 12 months
Primary Hypothesis
Intensive glycemic control with insulin in diabetic DM patients reduces intimal hyperplasia within the stented segment after percutaneous coronary revascularization
Secondary Hypothesis
The reduction in intimal hyperplasia is related to the degree of glycemic control ie HbA1c values and
Event-free survival is improved in patients treated with insulin
The pathophysiology of restenosis is viewed as a complex temporal sequence of interactions involving several cellular and mechanical factors including elastic recoil thrombosis intimal hyperplasia extra cellular matrix elaboration apoptosis oxidative stress and unfavorable arterial remodeling arterial shrinkage The exposure of subendothelial elements initiates platelet adhesion and activation Activated platelets at the site of injury secrete growth factors that release smooth muscle cells from growth inhibition and induce their proliferation and subsequent migration from the media to the intima Smooth muscle cell proliferation continues beyond the phase of platelet deposition Extracellular matrix is produced and secreted by smooth muscle cells that have migrated into the injured intimal zone This hypocellular matrix material forms the bulk of the intimal tissue Although mechanical factors such as early vessel elastic recoil may play a major role following balloon angioplasty this mechanism should not significantly affect the stented segments as the stent provides a rigid endovascular scaffold Similarly late arterial remodelling which has been postulated to be a significant factor for the development of restenosis after PCI should not have a major effect in the context of stents Therefore the major mechanism contributing to in-stent restenosis is aggressive intimal hyperplasia
Recent studies demonstrate that DM is characterized by diffuse intimal hyperplasia within the stented segment DM is an independent predictor of the volume of intimal hyperplasia within the stent The pattern of stent restenosis in patients with DM tends to be more diffuse and proliferative and therefore more likely to lead to total vessel occlusion This is significant because diffuse restenosis is difficult to manage with repeat percutaneous procedures
Hyperglycemia has been postulated to promote the restenotic process in diabetes by the following mechanisms i endothelial cell dysfunction ii increased platelet aggregation and thrombus formation iii dysregulation of growth factor expression iv abnormal extracellular matrix deposition v advanced isolation and products
Approaches to preventing stent restenosis have had limited effect Pharmacologic trials have universally failed to show a reduction in restenosis rates in human subjects Recent reports suggested radiation therapy brachytherapy especially applied locally either via catheters or through radioactive stents has a potential to reduce the proliferative response Although this approach holds great promise there are unresolved logistic issues safety issues and cost issues limiting wide-spread application
Preliminary studies of drug-eluting stents show initial promise in reducing restenosis rates However stent coatings can counteract the restenotic process only at points where the stent strut opposes the arterial wall and have little effect on neointimal tissue that can protrude between the struts and into the lumen Furthermore both brachytherapy and stent coatings only apply to the stented segments and the vessel whereas the arterial responses to balloon injury may also depend on flow characteristics ie rheology of the vessel Therefore alternative strategies that impact both local processes of the dilatation site and systematic processes on vessel remodelling and rheology are needed
Clinical trial data suggests that glycemic control may prevent restenosis A recent study of patients with type 2 diabetes undergoing PCI with stent demonstrated a significant reduction in both neointimal area and neointimal index among participants randomized to the glucose-lowering agent troglitazone Observational data from two registry studies indicate that diabetic patients with well-controlled hemoglobin A1c had lower rates of restenosis
Several lines of evidence suggest that insulin is safe and effective in controlling diabetes as well as reducing cardiovascular events The recently published DIGAMI Study in which patients with myocardial infarction were randomized to an insulin infusion followed by at least three months of intensified insulin therapy showed a 31 reduction mortality in patients receiving intensified therapy Subcutaneous insulin has been safely used to treat diabetes for almost 80 years Patients can easily learn to both inject and titrate insulin response to home capillary glucose measurements Greater than 85 of patients with type II diabetes who were started on insulin can achieve safe and effective metabolic control with one injection per day
Intravascular ultrasound is the most direct and sensitive technology available for measurement of intravascular hyperplasia volume within the stent It is the technology that is most likely to uncover a benefit of insulin in reducing restenosis if one exists This methodology will allow the research question to be answered with the smallest possible sample size Recent studies demonstrate that detailed cross-sectional analysis of intracoronary stents during motorized IVUS catheter pullback is feasible with excellent reproducibility safety and can be stored for off-line analysis Establishing a mechanistic link between glycemic control and restenosis will support the design of larger clinical studies evaluating clinical outcomes
Primary Study Question
Does intensive control of glucose levels with insulin in patients with DM reduce volume of intimal hyperplasia within the stented segment as evaluated by intravascular ultrasound IVUS at 6 months Secondary Study Question
Does intensive glycemic control with insulin reduce restenosis as evaluated by quantitative coronary angiography QCA at 6 months
Does intensive glycemic control with insulin prevent clinical events such as hospital admission for unstable angina and for congestive heart failure myocardial infarction stroke revascularization PCI CABG and death at 12 months
Primary Hypothesis
Intensive glycemic control with insulin in diabetic DM patients reduces intimal hyperplasia within the stented segment after percutaneous coronary revascularization
Secondary Hypothesis
The reduction in intimal hyperplasia is related to the degree of glycemic control ie HbA1c values and
Event-free survival is improved in patients treated with insulin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None