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A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE)

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ClinicalTrials.gov Identifier: NCT01959529
Recruitment Status : Completed
First Posted : October 10, 2013
Results First Posted : November 17, 2017
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: Diabetes
Diabetes Mellitus, Type 2
Interventions: Drug: insulin degludec
Drug: insulin glargine

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The trial was conducted at 438 sites in 20 countries as follows: Algeria: 6; Argentina: 4; Brazil: 10; Canada: 6; Croatia: 5; Greece: 6; India: 26; Italy: 10; Japan: 8; Republic of Korea: 4; Malaysia: 8; Mexico: 7; Poland: 8; Romania: 4; Russian Federation: 20; South Africa: 15; Spain: 6; Thailand: 6; United Kingdom: 8; United States: 271.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Insulin Degludec Subjects received insulin degludec (IDeg) 100 units/mL once daily (OD) subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with insulin aspart (IAsp) at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin twice daily (BID), the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.
Insulin Glargine Subjects received insulin glargine (IGlar) 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.

Participant Flow:   Overall Study
    Insulin Degludec   Insulin Glargine
STARTED   3818   3819 
Exposed   3809   3806 
COMPLETED   3742   3747 
NOT COMPLETED   76   72 
Adverse event (not hypoglycaemia)                0                1 
Lost to Follow-up                4                1 
Other                70                68 
Hypoglycaemia                1                1 
Lack of glycaemic control                1                1 



  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.
Baseline analysis was based on the full analysis set (FAS), which included all randomised subjects.

Reporting Groups
  Description
Insulin Degludec Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.
Insulin Glargine Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Total Total of all reporting groups

Baseline Measures
   Insulin Degludec   Insulin Glargine   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 3818   3819   7637 
Age 
[Units: Years]
Mean (Standard Deviation) 		 64.9  (7.3)   65.0  (7.5)   65.0  (7.4) 
Sex: Female, Male 
[Units: Participants]
Count of Participants 		     
Female      1422  37.2%      1437  37.6%      2859  37.4% 
Male      2396  62.8%      2382  62.4%      4778  62.6% 
HbA1c 
[Units: Percentage of HbA1c]
Mean (Standard Deviation) 		 8.44  (1.63)   8.41  (1.67)   8.43  (1.65) 


  Outcome Measures

1.  Primary:   Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke   [ Time Frame: From randomisation to individual end of trial date (maximum patient year observation: 2.75 years) ]
  Show Outcome Measure 1

2.  Secondary:   Number of EAC-confirmed Severe Hypoglycaemic Episodes   [ Time Frame: From randomisation to individual end of trial (maximum patient year observation: 2.75 years) ]
  Show Outcome Measure 2

3.  Secondary:   Occurrence of at Least One EAC Confirmed Severe Hypoglycaemic Episode Within a Subject (Yes/no)   [ Time Frame: From randomisation to individual end of trial date (maximum patient year observation: 2.75 years) ]
  Show Outcome Measure 3

4.  Secondary:   Change in Glycosylated Haemoglobin (HbA1c)   [ Time Frame: Randomisation to 24 months ]
  Show Outcome Measure 4


  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: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com


Publications of Results:


Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01959529     History of Changes
Other Study ID Numbers: EX1250-4080
2013-002371-17 ( EudraCT Number )
U1111-1141-7614 ( Other Identifier: WHO )
JapicCTI-142464 ( Registry Identifier: JAPIC )
First Submitted: October 8, 2013
First Posted: October 10, 2013
Results First Submitted: October 16, 2017
Results First Posted: November 17, 2017
Last Update Posted: January 19, 2018