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
  Purpose

This study is a phase 3b, multicentre, randomised, open label, parallel group study. A 4-week run-in period will be followed by a median of 6 years of treatment with study medication in addition to continuation of background glucose lowering therapy. Patients inadequately controlled on background metformin will be randomised to receive, in addition to metformin, either rosiglitazone or a sulfonylurea(glibenclamide, gliclazide or glimepiride) in a ratio of 1:1. Patients inadequately controlled on background SU will be randomised to receive, in addition to SU, either rosiglitazone or metformin in a ratio of 1:1. Equal numbers of patients receiving background metformin and SU at entry will be entered into the study.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Rosiglitazone
Drug: Sulfonylurea
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Long Term, Open Label, Randomised Study in Patients With Type 2 Diabetes, Comparing the Combination of Rosiglitazone and Either Metformin or Sulfonylurea With Metformin Plus Sulfonylurea on Cardiovascular Endpoints and Glycaemia

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 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) ] [ 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 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) ] [ 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.


Secondary Outcome Measures:
  • 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 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 ] [ 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]).

  • 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) ] [ Designated as safety issue: No ]
    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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    The observational follow-up (OFU) 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 OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    The observational follow-up (OFU) 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 OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    The OFU 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 OFU. 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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    The OFU 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 OFU. 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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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 that had the same Higher Level Group Term (HLGT) for fracture location, per participant.

  • 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) ] [ Designated as safety issue: No ]
    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 that had the same Higher Level Group Term (HLGT) for fracture location, per participant.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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 indicated fracture outcome was pre-specified in the CRF and included "Unknown" as a category. Fracture events with missing outcome data were reported as "Data unavailable."

  • 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) ] [ Designated as safety issue: No ]
    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 indicated fracture outcome was pre-specified in the CRF and included "Unknown" as a category. Fracture events with missing outcome data were reported as "Data unavailable."

  • 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) ] [ Designated as safety issue: No ]
    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 indicated fracture outcome was pre-specified in the CRF and included "Unknown" as a category. Fracture events with missing outcome data were reported as "Data unavailable."

  • 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) ] [ Designated as safety issue: No ]
    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. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.


Enrollment: 4447
Study Start Date: April 2001
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rosiglitazone in addition to background metformin
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.
Drug: Rosiglitazone
Rosiglitazone maximum 8 mg per day
Drug: Metformin
Metformin maximum permitted daily dose .
Experimental: rosiglitazone in addition to background sulfonylurea
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.
Drug: Rosiglitazone
Rosiglitazone maximum 8 mg per day
Drug: Sulfonylurea
Sulfonylurea (SU) maximum permitted daily dose
Active Comparator: Sulfonylurea in addition to background metformin
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 miconizied 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.
Drug: Sulfonylurea
Sulfonylurea (SU) maximum permitted daily dose
Drug: Metformin
Metformin maximum permitted daily dose .
Active Comparator: Metformin in addition to background sulfonylurea
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.
Drug: Sulfonylurea
Sulfonylurea (SU) maximum permitted daily dose
Drug: Metformin
Metformin maximum permitted daily dose .

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with type II diabetes mellitus as defined by 1999 World Health Organisation criteria.
  • Glycated haemoglobin (HbA1c) >7.0 % to = 9.0 % at visit 1.
  • Use of an oral glucose lowering agent for a minimum of 6 months prior to screening and unchanged for 2 months prior to screening.
  • Body mass index >25.0 kg/m2.

Exclusion Criteria:

  • Patients receiving any other glucose lowering therapy which is not metformin or a sulfonylurea.
  • Patients with systolic blood pressure >180 mmHg or diastolic blood pressure >105 mmHg.
  • Patients who have required the use of insulin for glycaemic control at any time in the past.
  • Hospitalisation for any major cardiovascular event in the last 3 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00379769

  Show 447 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Home PD, Pocock SJ, Beck-Nielsen H et al. The Lancet 2009; 373:2125-2135.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00379769     History of Changes
Other Study ID Numbers: BRL-049653/231
Study First Received: September 21, 2006
Results First Received: August 24, 2009
Last Updated: December 13, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
diabetes
CV outcomes
rosiglitazone
Type II diabetes
sulfonylurea
RECORD
metformin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Rosiglitazone
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014