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

• Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded.
  
  
• 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) ] [ Designated as safety issue: No ]
  All deaths identified during the original record study and discovered after the re-adjudication efforts began were included.
  
  
• Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurence 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) ] [ Designated as safety issue: No ]
  IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin.
  
  
• Independent Re-adjudication Outcome: Number of Participants With a First Occurence 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) ] [ Designated as safety issue: No ]
  Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.
  
  
• 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) ] [ Designated as safety issue: No ]
  The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as "unknown deaths," but were counted as CV deaths for the analysis of this endpoint.
  
  
• 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) ] [ Designated as safety issue: No ]
  The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths.
  
  
• 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) ] [ Designated as safety issue: No ]
  The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme >= 2x the ULN or CK > 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI.
  
  
• 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) ] [ Designated as safety issue: No ]
  The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia.
  
  
• 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) ] [ Designated as safety issue: No ]
  Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke.
  
  
• 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) ] [ Designated as safety issue: No ]
  The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.
  
  

• Number of Participants With Cardiovascular Events and All-cause Deaths [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  Composites of participants with first cardiovascular (CV) hospitalisations and CV death or all-cause death and individual first events of acute myocardial infarction (MI) , stroke, congestive heart failure (CHF), CV death, and all-cause death.
  
  
• Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  The total number of events for individual components of cardiovascular (CV) hospitalisations and cardiovascular deaths were recorded. MI, myocardial infarction.
  
  
• Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  Participants with first cardiovascular death (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) were recorded by study stratum.
  
  
• Number of Participants With CV/Microvascular Events [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  The number of participants with first cardiovascular or microvascular events (renal, foot, eye) were recorded.
  
  
• Number of Participants With Glycaemic Failure Events [ Time Frame: Baseline through to end of randomised dual therapy ] [ Designated as safety issue: No ]
  Failure of glycaemic control was defined as two consecutive HbA1c values of ≥8.5 percent, or HbA1c ≥8.5percent at a single visit, after which the subject was either moved to the post-randomised treatment phase or triple therapy was started.
  
  
• Number of Participants With Addition of Third Oral Agent/Switch to Insulin [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  The number of participants with addition of a third oral agent or switch to insulin from randomised dual combination treatment were recorded.
  
  
• The Number of Participants Starting Insulin at Any Time During the Study [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
  The number of participants starting insulin at any time during the study was recorded.
  
  
• Model Adjusted Change From Baseline in HbA1c at Month 60 [ Time Frame: Baseline and Month 60 of randomised dual therapy treatment period ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value.
  
  
• 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 ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in fasting plasma glucose was calculated as the value at Month 60 minus the Baseline value.
  
  
• 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 ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in insulin and pro-insulin was calculated as the value at Month 60 minus the Baseline value.
  
  
• 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 ] [ Designated as safety issue: No ]
  Number of responders, i.e., participants meeting glycaemic targets (HbA1c less than or equal to 7 percent, FPG less than or equal to 7 mmol/L)
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC, LDL cholesterol, HDL cholesterol, triglycerides, and FFAs was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholersterol (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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in Apo-B was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in urinary albumin creatinine ratio was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• Model Adjusted Change From Baseline in Body Weight at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in body weight was calculated as the value at Month 60 minus the Baseline value.
  
  
• Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in alanine aminotransferase was calculated as the value at Month 60 minus the Baseline value.
  
  
• Model Adjusted Change From Baseline in Waist Circumference at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in waist circumference was calculated as the value at Month 60 minus the Baseline value.
  
  
• 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 ] [ Designated as safety issue: No ]
  Model adjusted (adjusted for any imbalances in the baseline values between within treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value.
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in C-Reactive Protein was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in fibrinogen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  
• 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 ] [ Designated as safety issue: No ]
  The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in plasminogen activator inhibitor-1 (PAI-1) antigen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
  
  

A RECORD follow-up study is being performed to monitor the incidence of cancer and bone fractures in RECORD patients for a period of 4 years after the end of the main RECORD study (2008 - 2012).