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Comparison of Insulin Detemir, Insulin Aspart and Biphasic Insulin Aspart 30 With OAD Treatment in Type 2 Diabetes (4T)

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ClinicalTrials.gov Identifier: NCT00184600
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : July 25, 2011
Last Update Posted : March 9, 2017
Sponsor:
Information provided by (Responsible Party):

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Diabetes
Diabetes Mellitus, Type 2
Interventions: Drug: biphasic insulin aspart
Drug: insulin detemir
Drug: insulin aspart

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
58 sites across the United Kingdom and Ireland. Recruitment period: November 2004-August 2006

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible subjects continued their current oral anti-diabetic drug (OAD) treatment (metformin and/or sulphonylurea) without changing the dose throughout the trial. Subjects were asked not to alter their current diet and activities throughout the trial unless clinically necessary. Subjects fasted from 22:00 the evening prior to randomisation.

Reporting Groups
  Description
Insulin Detemir (Basal Insulin) Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen
Insulin Aspart (Prandial Insulin) Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen
Biphasic Insulin Aspart 30 (Biphasic Insulin) Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen

Participant Flow:   Overall Study
    Insulin Detemir (Basal Insulin)   Insulin Aspart (Prandial Insulin)   Biphasic Insulin Aspart 30 (Biphasic Insulin)
STARTED   234   239   235 
COMPLETED   189   188   201 
NOT COMPLETED   45   51   34 
Adverse Event                9                0                5 
Death                3                9                7 
Lack of Efficacy                3                1                3 
Lost to Follow-up                4                6                1 
Protocol Violation                2                2                3 
Withdrawal by Subject                20                28                12 
Unclassified                4                5                3 



  Baseline Characteristics

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
Insulin Detemir (Basal Insulin) Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen
Insulin Aspart (Prandial Insulin) Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen
Biphasic Insulin Aspart 30 (Biphasic Insulin) Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Total Total of all reporting groups

Baseline Measures
   Insulin Detemir (Basal Insulin)   Insulin Aspart (Prandial Insulin)   Biphasic Insulin Aspart 30 (Biphasic Insulin)   Total 
Overall Participants Analyzed 
[Units: Participants]
 234   239   235   708 
Age 
[Units: Years]
Mean (Standard Deviation)
 61.87  (9.97)   61.60  (10.54)   61.67  (8.93)   61.7  (9.8) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      91  38.9%      87  36.4%      76  32.3%      254  35.9% 
Male      143  61.1%      152  63.6%      159  67.7%      454  64.1% 
Race/Ethnicity, Customized 
[Units: Participants]
       
White   218   214   221   653 
Mixed   2   4   1   7 
Asian / Asian British   9   15   11   35 
Black / Black British   2   5   2   9 
Other   3   1   0   4 
Smoking [1] 
[Units: Participants]
       
Non Smoker, Never Smoked   106   88   82   276 
Ex Smoker   95   108   120   323 
Current Smoker   33   43   33   109 
[1] Identifying participants as smokers/non-smokers
Oral Anti-Diabetic Drugs (OADs) [1] 
[Units: Participants]
       
Metformin   2   0   4   6 
Sulphonylurea   8   12   10   30 
Metformin + Sulphonylurea   224   227   221   672 
[1] Identifying which OAD (oral anti-diabetic drug) treatment the participant is on
Diabetic complication, Retinopathy [1] 
[Units: Participants]
       
Yes   43   45   34   122 
No   191   194   201   586 
[1] Diabetic complication at baseline
Diabetic complication, Neuropathy [1] 
[Units: Participants]
       
Yes   39   55   41   135 
No   195   184   194   573 
[1] Diabetic complication at baseline
Diabetic complication, Nephropathy [1] 
[Units: Participants]
       
Yes   23   24   21   68 
No   211   215   214   640 
[1] Diabetic complication at baseline
Diabetic complication, Macroaniopathy [1] 
[Units: Participants]
       
Yes   44   42   52   138 
No   190   197   183   570 
[1] Diabetic complication at baseline
Duration of diabetes [1] 
[Units: Years]
Median (Inter-Quartile Range)
 9 
 (6 to 12) 
 9 
 (6 to 14) 
 9 
 (6 to 12) 
 9 
 (6 to 13) 
[1] Number of years since diagnosis
Alcohol [1] 
[Units: Units]
Median (Inter-Quartile Range)
 4 
 (2 to 12) 
 5 
 (2 to 12) 
 6 
 (2 to 12) 
 5 
 (2 to 12) 
[1] Number of units consumed weekly. One unit of alcohol = 10ml pure alcohol by volume or 8g by weight.
Weight [1] 
[Units: Kg]
Mean (Standard Deviation)
 85.52  (16.25)   84.92  (14.43)   86.91  (16.82)   85.8  (15.9) 
[1] Weight of participants
Body Mass Index (BMI) [1] 
[Units: Kg/m^2]
Mean (Standard Deviation)
 29.82  (4.59)   29.74  (4.51)   30.34  (4.73)   29.8  (4.6) 
[1] BMI of participants
Waist [1] 
[Units: Cm]
Mean (Standard Deviation)
       
Men   104  (12)   102  (11)   104  (12)   103  (12) 
Women   97  (12)   100  (11)   98  (13)   98  (12) 
[1] Waist circumference of participants
Eight-point Capillary Plasma Glucose Profiles 
[Units: mg/dL]
Mean (Standard Deviation)
       
All time pointsexcluding 3 am   196  (43)   200  (49)   202  (47)   200  (47) 
Fasting plasma   171  (47)   173  (49)   175  (50)   173  (49) 
Postprandial   223  (50)   227  (56)   229  (54)   227  (54) 
At 3 am   164  (56)   164  (59)   171  (58)   166  (58) 


  Outcome Measures

1.  Primary:   HbA1c (Glycosylated Haemoglobin) at Month 12   [ Time Frame: Baseline, Month 12 ]

2.  Primary:   HbA1c (Glycosylated Haemoglobin) at Month 36   [ Time Frame: Baseline, Month 36 ]

3.  Secondary:   Percentage of Participants (Total Participants and the Subset of Participants Who Did Not Have an Hypoglycaemic Episode) Achieving a Month 12 Value in HbA1c Below or Equal to 6.5%   [ Time Frame: Month 12 ]

4.  Secondary:   Percentage of Participants Achieving a Month 36 Value in HbA1c Below or Equal to 6.5%   [ Time Frame: Month 36 ]

5.  Secondary:   Number of Hypoglycaemic Events Per Participant Per Year at Month 12 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5%   [ Time Frame: Month 12 ]

6.  Secondary:   Number of Hypoglycaemic Events Per Participant Per Year at Month 36 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5%   [ Time Frame: Month 36 ]

7.  Secondary:   Percentage of Participants Who Required A Second Insulin Therapy by Month 12   [ Time Frame: Month 12 ]

8.  Secondary:   Percentage of Participants Who Required A Second Insulin Therapy by Month 36   [ Time Frame: Month 36 ]

9.  Secondary:   Change From Baseline in Body Weight at Month 12   [ Time Frame: Week 0 (baseline), month 12 ]

10.  Secondary:   Change From Baseline in Body Weight at Month 36   [ Time Frame: Week 0 (baseline), month 36 ]

11.  Secondary:   Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months   [ Time Frame: Baseline, month 12 ]

12.  Secondary:   Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months   [ Time Frame: Baseline, month 36 ]

13.  Secondary:   Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 12 Months   [ Time Frame: Month 12 ]

14.  Secondary:   Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 36 Months   [ Time Frame: Month 36 ]

15.  Secondary:   Number of Participants Having an 'Other' Adverse Event   [ Time Frame: Up to month 37 (36 months of treatment plus 1 month follow-up) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com


Publications of Results:

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00184600     History of Changes
Other Study ID Numbers: NN304-1613
2004-000514-38 ( EudraCT Number )
First Submitted: September 13, 2005
First Posted: September 16, 2005
Results First Submitted: May 10, 2011
Results First Posted: July 25, 2011
Last Update Posted: March 9, 2017