RECORD: Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00379769
First received: September 21, 2006
Last updated: December 13, 2013
Last verified: December 2013
Results First Received: August 24, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Rosiglitazone
Drug: Sulfonylurea
Drug: Metformin

  Participant Flow
  Hide 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 RECORD study ran from April 2001 through December 2008. Results are presented in the non-re-adjudicated outcome measures (OMs). An independent patient-level re-adjudication of mortality, non-fatal myocardial infarction, and non-fatal stroke began on January 2011 and ran through March 2012. The results are presented in the re-adjudicated OMs.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The RECORD observational follow-up (OFU) started at the end of the RECORD study and ran through December 2012. OFU was designed to collect cancer and bone fracture data. Participants were not provided with study medication in the OFU. Data are presented for the entire study (RECORD + OBF) and for OFU alone in the observational OMs.

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Participant Flow for 2 periods

Period 1:   Main Study
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
STARTED     1117     1105     1103     1122     0     0  
COMPLETED     939     906     896     892     0     0  
NOT COMPLETED     178     199     207     230     0     0  
Death                 57                 67                 54                 72                 0                 0  
Adverse Event                 5                 8                 10                 11                 0                 0  
Lost to Follow-up                 29                 29                 25                 26                 0                 0  
Withdrawal by Subject                 46                 56                 72                 70                 0                 0  
Moved to survival status follow-up only                 27                 25                 32                 36                 0                 0  
Participant moved                 3                 2                 3                 3                 0                 0  
Poor compliance                 3                 2                 2                 1                 0                 0  
Prohibited glucose lowering medication                 0                 3                 0                 1                 0                 0  
Site closed                 4                 4                 4                 8                 0                 0  
Entry criteria violation                 0                 0                 1                 1                 0                 0  
Participant did not take study drug                 0                 0                 1                 0                 0                 0  
Physician Decision                 2                 2                 1                 1                 0                 0  
Participant completed study at visit 27                 1                 0                 0                 0                 0                 0  
Personal reasons                 1                 0                 0                 0                 0                 0  
Risk of heart failure                 0                 1                 0                 0                 0                 0  
Investigator refused to log temperature                 0                 0                 1                 0                 0                 0  
Reason unspecified                 0                 0                 1                 0                 0                 0  

Period 2:   Observational Follow-up
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
STARTED     0     0     0     0     1280 [1]   1250 [2]
COMPLETED     0     0     0     0     1131     1102  
NOT COMPLETED     0     0     0     0     149     148  
Death                 0                 0                 0                 0                 78                 70  
Adverse Event                 0                 0                 0                 0                 1                 0  
Lost to Follow-up                 0                 0                 0                 0                 25                 27  
Withdrawal by Subject                 0                 0                 0                 0                 12                 12  
Entered into Another Clinical Trial                 0                 0                 0                 0                 18                 22  
Physician Decision                 0                 0                 0                 0                 8                 8  
Site Closed Early                 0                 0                 0                 0                 6                 7  
Participant Moved                 0                 0                 0                 0                 0                 1  
Unknown; Reason Not Provided                 0                 0                 0                 0                 1                 1  
[1] 665 from “RSG in Addition to Background MET” arm; 615 from “RGS in Addition to Background SU” arm.
[2] 647 from “SU in Addition to Background MET” arm; 603 from “MET in Addition to Background SU” arm.



  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
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Total Total of all reporting groups

Baseline Measures
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Total  
Number of Participants  
[units: participants]
  1117     1105     1103     1122     4447  
Age  
[units: years]
Mean ± Standard Deviation
  57.0  ± 8.02     57.2  ± 8.14     59.8  ± 8.26     59.7  ± 8.23     58.4  ± 8.27  
Gender  
[units: participants]
         
Female     516     521     562     554     2153  
Male     601     584     541     568     2294  
Race/Ethnicity, Customized  
[units: participants]
         
White     1105     1087     1095     1112     4399  
Black     3     6     2     3     14  
Oriental     4     2     5     7     18  
Aboriginal     1     0     0     0     1  
African     1     0     0     0     1  
Asian     1     2     1     0     4  
Egyptian     1     0     0     0     1  
Gipsy     1     0     0     0     1  
Indian     0     1     0     0     1  
Maori     0     1     0     0     1  
Middle East Hible     0     1     0     0     1  
Pacific Islander     0     1     0     0     1  
Polynesian     0     1     0     0     1  
Sri Lankan     0     2     0     0     2  
Tahitian     0     1     0     0     1  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

2.  Primary:   Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

3.  Primary:   Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

4.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

5.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

6.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

7.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

8.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

9.  Primary:   Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

10.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

11.  Secondary:   Number of Participants With Cardiovascular Events and All-cause Deaths   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

12.  Secondary:   Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

13.  Secondary:   Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

14.  Secondary:   Number of Participants With CV/Microvascular Events   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

15.  Secondary:   Number of Participants With Glycaemic Failure Events   [ Time Frame: Baseline through to end of randomised dual therapy ]

16.  Secondary:   Number of Participants With Addition of Third Oral Agent/Switch to Insulin   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

17.  Secondary:   The Number of Participants Starting Insulin at Any Time During the Study   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

18.  Secondary:   Model Adjusted Change From Baseline in HbA1c at Month 60   [ Time Frame: Baseline and Month 60 of randomised dual therapy treatment period ]

19.  Secondary:   Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

20.  Secondary:   Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

21.  Secondary:   Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

22.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

23.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

24.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

25.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

26.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

27.  Secondary:   Model Adjusted Change From Baseline in Body Weight at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

28.  Secondary:   Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

29.  Secondary:   Model Adjusted Change From Baseline in Waist Circumference at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

30.  Secondary:   Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

31.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

32.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

33.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

34.  Secondary:   Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

35.  Secondary:   Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

36.  Secondary:   Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

37.  Secondary:   Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

38.  Secondary:   Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

39.  Secondary:   Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

40.  Secondary:   Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

41.  Secondary:   Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

42.  Secondary:   Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

43.  Secondary:   Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

44.  Secondary:   Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

45.  Secondary:   Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

46.  Secondary:   Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

47.  Secondary:   Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

48.  Secondary:   Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]
  Hide Outcome Measure 48

Measure Type Secondary
Measure Title Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown).
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
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.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined  
[units: participants]
   
Any H/UA/FF event, overall, n=2220, 2227     86     46  
Any H/UA/FF event, male, n=1142, 1152     28     15  
Any H/UA/FF event, female, n=1078, 1075     58     31  
High morbidity fractures, overall, n=2220, 2227     5     1  
High morbidity fractures, male, n=1142, 1152     0     0  
High morbidity fractures, female, n=1078, 1075     5     1  
Non-high morbidity fractures, overall, n=2220, 222     15     4  
Non-high morbidity fractures, male, n=1142, 1152     2     3  
Non-high morbidity fractures, female, n=1078, 1075     13     1  

No statistical analysis provided for Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined



49.  Secondary:   Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

50.  Secondary:   Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

51.  Secondary:   Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

52.  Secondary:   Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

53.  Secondary:   Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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