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Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)

This study has been completed.
Sponsor:
Collaborators:
SmithKline Beecham
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00032487
First received: March 21, 2002
Last updated: March 7, 2014
Last verified: March 2014
Results First Received: September 10, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Insulin
Drug: Glimepiride
Drug: Rosiglitazone
Drug: Metformin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Twenty Veterans Affairs Medical Centers (VAMCs) were selected to participate in this cooperative study. The recruitment period was from 12/01/00 to 05/31/03.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A patient had to meet all the screening criteria for eligibility and had to sign a consent form with blood samples and meet all entry criteria for pre-randomization testing. Once the patient was deemed appropriate for the study, Hines completed the randomization assignment.

Reporting Groups
  Description
Standard Glycemic Control Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs
Intensive Glycemic Control Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1

Participant Flow:   Overall Study
    Standard Glycemic Control     Intensive Glycemic Control  
STARTED     899     892  
COMPLETED     760     772  
NOT COMPLETED     139     120  
Withdrawal by Subject                 67                 43  
Adverse Event                 3                 7  
Lost to Follow-up                 57                 58  
Had other reason                 12                 12  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm 1/Standard Glycemic Control Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs
Arm 2/Intensive Glycemic Control Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Standard glycemic control
Total Total of all reporting groups

Baseline Measures
    Arm 1/Standard Glycemic Control     Arm 2/Intensive Glycemic Control     Total  
Number of Participants  
[units: participants]
  899     892     1791  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     606     612     1218  
>=65 years     293     280     573  
Age  
[units: years]
Mean ± Standard Deviation
  60.3  ± 9.0     60.5  ± 9.0     60.4  ± 9.0  
Gender  
[units: participants]
     
Female     26     26     52  
Male     873     866     1739  
Region of Enrollment  
[units: participants]
     
United States     899     892     1791  



  Outcome Measures
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1.  Primary:   Primary Major Macrovascular Events   [ Time Frame: Post baseline time to the first major macrovascular event up to 82 months ]
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Measure Type Primary
Measure Title Primary Major Macrovascular Events
Measure Description Myocardial infarction (MI), intervention for coronary artery or Peripheral Vascular Disease (PVD), severe inoperable Coronary Artery Disease (CAD), new or worsening Congestive Heart Failure (CHF), stroke, Cardiovascular (CV) death, or amputation for ischemic gangrene.
Time Frame Post baseline time to the first major macrovascular event up to 82 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm 1 Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs
Arm 2 Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1

Measured Values
    Arm 1     Arm 2  
Number of Participants Analyzed  
[units: participants]
  899     892  
Primary Major Macrovascular Events  
[units: participants]
  264     235  


Statistical Analysis 1 for Primary Major Macrovascular Events
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Log Rank
P Value [4] <0.05
Cox Proportional Hazard [5] 0.79
95% Confidence Interval ( .79 to .99 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  It was hypothesized 21% reduction in intensive glycemic control group compared to standard control group on primary cardiovascular composite outcomes.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  The statistical analysis tested was for equivalence. We assumed 86% power with 21% of effect size and the sample size 1700 with 5% drop out rate.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  N/A
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  N/A
[5] Other relevant estimation information:
  N/A



2.  Secondary:   Secondary Endpoint   [ Time Frame: Post baseline time to first event up to 82 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Our study had several limitations. Since we were studying veterans, the patients were predominantly men, and extrapolation of our findings to women must be done with caution.Changes in therapeutic agents have occurred since the design of our protocol


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