Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00032487
Status:
COMPLETED
Last Update Posted:
2017-03-30
First Post:
2002-03-21
Brief Title:
Glycemic Control and Complications in Diabetes Mellitus Type 2 VADT
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 465 - Glycemic Control and Complications in Diabetes Mellitus Type 2 VADT
Status:
COMPLETED
Status Verified Date:
2017-02
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:
VADT
Brief Summary:
This study is a prospective 2-arm randomized controlled trial to determine whether glycemic control achieved through intensification of treatment is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone The study consists of a two-year accrual period and five years of follow-up 7 years total of 1700 patients across 20 centers We have powered the study to detect a 21 reduction in the primary event rate Additional study goals are to determine whether the expenditures discomfort and adverse effects associated with intensive intervention are justified in terms of their clinical benefits considering both macrovascular and microvascular complications
Detailed Description:
Primary Hypothesis Intensive glycemic control reduces major macrovascular morbidity and mortality compared to standard glycemic control in type 2 diabetics who have failed simple therapy
Secondary Hypotheses Intensive glycemic control compared to standard glycemic control reduces other macrovascular morbidity and total mortality
Intervention The intervention is tight glycemic control aiming at normalization of HbA1c This will be achieved through stepped care therapy using all categories of tools available to most diabetologists These categories include patient education of diabetes control eg diet exercise etc oral diabetes medications and insulin All drugs to be used are approved Specific agents will be used within the different classes to promote consistency across sites
The comparison is standard control aiming at HbA1c of 8 - 9 The same agents will be used but at reduced doses
The general approach to the stepped care treatment protocol is to treat both groups with the same agents but at different intensities doses taking into account intolerancecontraindications The sequence of steps is shown below
STEP 1 Either Metformin obese or Glimepiride leanin combination with Rosiglitazone STEP 2 Insulin STEP 3 Increase doses in STEPS 12 in the Standard group Since the Intensive group is already at maximal doses of oral agents they will intensify insulin and may add AcarboseMiglitol
STEP 4 For standard proceed as in STEP 3 for Intensive Intensives will use multiple daily injection MDI of insulin STEP 5 Tool Box Miscellaneous agents tailored to the individual patient
Primary Outcomes Time to one of the following major macrovascular events myocardial infarction stroke new or worsening congestive heart failure amputation for ischemic gangrene invasive intervention for coronary artery or peripheral vascular disease inoperable coronary artery disease or cardiovascular death
Secondary Outcomes Angina transient ischemic attack intermittent claudication critical limb ischemia and total mortality
Study Abstract A quarter of the patients treated by the Department of Veterans Affairs VA Health Administration have type 2 diabetes mellitus DM The costs of care for the treatment of patients with type 2 DM are extremely high both in treatment expenditures for the metabolic disorder and for the care of end-organ complications Although patients initially respond to diet and oral agent treatment most eventually need insulin to near-normalize their glucose level as the disease is characterized by progressive loss of insulin secretory capacity
After several clinical trials in both type 1 and type 2 DM there is a reasonable certainty that about half of the incidence and rate of progression of indicators of microvascular complications retinopathy nephropathy and neuropathy can be prevented or delayed by achieving and maintaining near-normalization of glycemic levels Consequently there has been a uniform trend in recent guidelines to advise a near-normalization of glycemic levels in both type 1 and type 2 DM Note however that the clinical consequences of microvascular deterioration are dependent not only on glycemic levels but also on the duration of the disease With the early onset of diabetes typical in type 1 patients there is sufficient time for development of clinical microvascular complications and prevention of these complications is a goal of treatment in type 1 diabetics In contrast the prevalence of hard clinical endpoints indicative of microangiopathy such as renal failure or blindness is very low in patients in whom the disease is diagnosed after the 5th decade the greatest age of prevalence of patients with type 2 DM in this country Furthermore microvascular complications can be minimized by the well-established benefits of blood pressure and lipid control as well as by therapeutic intervention photocoagulation cataract extraction Since the costs and efforts necessary to reach near-normal levels of glycemia are very high there is a need to determine the costbenefit ratios of such expenditures in the population subject to type 2 diabetes namely patients in their 6th to 8th decades of life
In contrast with the late and relatively infrequent appearance of clinical endpoints of microangiopathy macrovascular complications ie coronary heart disease and peripheral vascular disease are responsible for the overwhelming majority of the mortality morbidity and treatment costs in the American population of type 2 diabetics even more so in the older VA diabetic population In the recently concluded United Kingdom Prospective Diabetes Study UKPDS on type 2 DM macrovascular mortality was 70 times higher than that of microvascular mortality Intervention studies to determine the effect of rigorous glycemic control on these macrovascular events are inconclusive and contradictory Intensive treatment in patients who are newly diagnosed has failed to demonstrate a beneficial effect of tight control on cardiovascular complications The few studies conducted in later stages of the disease ie in patients requiring insulin treatment alone or in combination with oral agents have been conflicting and indeterminate
The decision on intensity of treatment is further compromised by current recommendations to attenuate glycemic control goals especially when usage of insulin is required both in patients with the common comorbidities of overweight or preexisting cardiovascular disease and in those in the later decades of life These concerns are based on fears that intensive insulin treatment might be associated with weight gain increased cardiovascular risk factors hypertriglyceridemia dyslipidemia hyperinsulinemia and insulin resistance and adverse effects of recurrent hypoglycemic events The prevalent level of glycemic control in insulin-treated type 2 diabetics is relatively poor likely due to a combination of practical difficulties and the uncertainties of what are the safe and effective glycemic goals There is no long-term study currently being done in the high-risk population typical of the patient population in the VA Before the Department of Veterans Affairs devotes considerable resources to a widespread intervention a quarter of patients that may be of little value and might even be counterproductive a trial to determine the value of the intervention is mandated It is expected that CSP 465 will provide the scientific data on which the VA can base clinical treatment of Type II diabetes
CSP 465 is a prospective 2-arm randomized controlled trial to determine whether glycemic control achieved through intensification of treatment is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone The study consists of a two-year accrual period and five years of follow-up 7 years total of 1700 patients across 20 centers We have powered the study to detect a 25 reduction in the primary event rate Additional study goals are to determine whether the expenditures discomfort and adverse effects associated with intensive intervention are justified in terms of their clinical benefits considering both macrovascular and microvascular complications
Main ManuscriptDuckworth W Abraira C Moritz T Reda D Emanuele N et al VADT investigators Glucose Control and Complications in the VA Diabetes Trial VADT N Eng J of Med 360129-139 2009
Secondary Hypotheses Intensive glycemic control compared to standard glycemic control reduces other macrovascular morbidity and total mortality
Intervention The intervention is tight glycemic control aiming at normalization of HbA1c This will be achieved through stepped care therapy using all categories of tools available to most diabetologists These categories include patient education of diabetes control eg diet exercise etc oral diabetes medications and insulin All drugs to be used are approved Specific agents will be used within the different classes to promote consistency across sites
The comparison is standard control aiming at HbA1c of 8 - 9 The same agents will be used but at reduced doses
The general approach to the stepped care treatment protocol is to treat both groups with the same agents but at different intensities doses taking into account intolerancecontraindications The sequence of steps is shown below
STEP 1 Either Metformin obese or Glimepiride leanin combination with Rosiglitazone STEP 2 Insulin STEP 3 Increase doses in STEPS 12 in the Standard group Since the Intensive group is already at maximal doses of oral agents they will intensify insulin and may add AcarboseMiglitol
STEP 4 For standard proceed as in STEP 3 for Intensive Intensives will use multiple daily injection MDI of insulin STEP 5 Tool Box Miscellaneous agents tailored to the individual patient
Primary Outcomes Time to one of the following major macrovascular events myocardial infarction stroke new or worsening congestive heart failure amputation for ischemic gangrene invasive intervention for coronary artery or peripheral vascular disease inoperable coronary artery disease or cardiovascular death
Secondary Outcomes Angina transient ischemic attack intermittent claudication critical limb ischemia and total mortality
Study Abstract A quarter of the patients treated by the Department of Veterans Affairs VA Health Administration have type 2 diabetes mellitus DM The costs of care for the treatment of patients with type 2 DM are extremely high both in treatment expenditures for the metabolic disorder and for the care of end-organ complications Although patients initially respond to diet and oral agent treatment most eventually need insulin to near-normalize their glucose level as the disease is characterized by progressive loss of insulin secretory capacity
After several clinical trials in both type 1 and type 2 DM there is a reasonable certainty that about half of the incidence and rate of progression of indicators of microvascular complications retinopathy nephropathy and neuropathy can be prevented or delayed by achieving and maintaining near-normalization of glycemic levels Consequently there has been a uniform trend in recent guidelines to advise a near-normalization of glycemic levels in both type 1 and type 2 DM Note however that the clinical consequences of microvascular deterioration are dependent not only on glycemic levels but also on the duration of the disease With the early onset of diabetes typical in type 1 patients there is sufficient time for development of clinical microvascular complications and prevention of these complications is a goal of treatment in type 1 diabetics In contrast the prevalence of hard clinical endpoints indicative of microangiopathy such as renal failure or blindness is very low in patients in whom the disease is diagnosed after the 5th decade the greatest age of prevalence of patients with type 2 DM in this country Furthermore microvascular complications can be minimized by the well-established benefits of blood pressure and lipid control as well as by therapeutic intervention photocoagulation cataract extraction Since the costs and efforts necessary to reach near-normal levels of glycemia are very high there is a need to determine the costbenefit ratios of such expenditures in the population subject to type 2 diabetes namely patients in their 6th to 8th decades of life
In contrast with the late and relatively infrequent appearance of clinical endpoints of microangiopathy macrovascular complications ie coronary heart disease and peripheral vascular disease are responsible for the overwhelming majority of the mortality morbidity and treatment costs in the American population of type 2 diabetics even more so in the older VA diabetic population In the recently concluded United Kingdom Prospective Diabetes Study UKPDS on type 2 DM macrovascular mortality was 70 times higher than that of microvascular mortality Intervention studies to determine the effect of rigorous glycemic control on these macrovascular events are inconclusive and contradictory Intensive treatment in patients who are newly diagnosed has failed to demonstrate a beneficial effect of tight control on cardiovascular complications The few studies conducted in later stages of the disease ie in patients requiring insulin treatment alone or in combination with oral agents have been conflicting and indeterminate
The decision on intensity of treatment is further compromised by current recommendations to attenuate glycemic control goals especially when usage of insulin is required both in patients with the common comorbidities of overweight or preexisting cardiovascular disease and in those in the later decades of life These concerns are based on fears that intensive insulin treatment might be associated with weight gain increased cardiovascular risk factors hypertriglyceridemia dyslipidemia hyperinsulinemia and insulin resistance and adverse effects of recurrent hypoglycemic events The prevalent level of glycemic control in insulin-treated type 2 diabetics is relatively poor likely due to a combination of practical difficulties and the uncertainties of what are the safe and effective glycemic goals There is no long-term study currently being done in the high-risk population typical of the patient population in the VA Before the Department of Veterans Affairs devotes considerable resources to a widespread intervention a quarter of patients that may be of little value and might even be counterproductive a trial to determine the value of the intervention is mandated It is expected that CSP 465 will provide the scientific data on which the VA can base clinical treatment of Type II diabetes
CSP 465 is a prospective 2-arm randomized controlled trial to determine whether glycemic control achieved through intensification of treatment is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone The study consists of a two-year accrual period and five years of follow-up 7 years total of 1700 patients across 20 centers We have powered the study to detect a 25 reduction in the primary event rate Additional study goals are to determine whether the expenditures discomfort and adverse effects associated with intensive intervention are justified in terms of their clinical benefits considering both macrovascular and microvascular complications
Main ManuscriptDuckworth W Abraira C Moritz T Reda D Emanuele N et al VADT investigators Glucose Control and Complications in the VA Diabetes Trial VADT N Eng J of Med 360129-139 2009
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