RECORD: Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00379769

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 Type II Diabetes	Drug: Rosiglitazone in addition to background sulfonylurea Drug: Rosiglitazone in addition to background metformin Drug: Sulfonylurea in addition to background metformin Drug: Metformin in addition to background sulfonylurea	Phase III

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:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Rosiglitazone Rosiglitazone Maleate Metformin Metformin hydrochloride

U.S. FDA Resources

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.

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 treatment groups) change from baseline in HbA1c was calculated as 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 treatment groups) change from baseline in fasting plasma glucose was calculated as 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 treatment groups) change from baseline in insulin and pro-insulin was calculated as 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 values between treatment groups) ratio to baseline in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the value at month 60 to the value at baseline and expressed as a percent change from baseline.
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids 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 values between treatment groups) ratio to baseline in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and free fatty acids were calculated as the ratio of the value at month 60 to the value at baseline and expressed as percent change from baseline.
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholersterol: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 values between treatment groups) ratio to baseline in total cholesterol:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the value at month 60 to the value at baseline and expressed as a percent change from baseline.
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 values between treatment groups) ratio to baseline in Apo-B was calculated as the ratio of the value at month 60 to the ratio of the value at baseline and expressed as a percentage change from baseline.
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 values between treatment groups) ratio to baseline in urinary albumin creatinine ratio was calculated as the ratio of the value at month 60 to the ratio of the value at baseline and expressed as a percent change from baseline.
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 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 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 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 treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value.
Model Adjusted Change From Baseline in C- Reactive Protein (CRP) 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 treatment groups) change from baseline in CRP was calculated as the value at Month 60 minus the Baseline value.
Model Adjusted Change From Baseline in Fibrinogen 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 treatment groups) change from baseline in fibrinogen was calculated as the value at Month 60 minus the Baseline value.
Model Adjusted Change From Baseline in 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 ]
Model adjusted (adjusted for any imbalances in the baseline values between treatment groups) change from baseline in PAI-1 antigen was calculated as the value at Month 60 minus the Baseline value..

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
Active Comparator: add-on medication 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 an SU (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.	Drug: 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 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: 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: 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.

Arms

Assigned Interventions

Active Comparator: add-on medication

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 an SU (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.

Drug: 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 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: 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: 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.

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).

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

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:	August 6, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency