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

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”

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.

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).

Intervention(s) in this Clinical Trial

• 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, Groups and Cohorts in this Clinical Trial

• 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.

Primary Measures

• Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No

Secondary Measures

• Number of Participants With Cardiovascular Events and All-cause Deaths
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No
• Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No
• Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No
• Number of Participants With CV/Microvascular Events
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No
• Number of Participants With Glycaemic Failure Events
  • Time Frame: Baseline through to end of randomised dual therapy
    Safety Issue?: No
• Number of Participants With Addition of Third Oral Agent/Switch to Insulin
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No
• The Number of Participants Starting Insulin at Any Time During the Study
  • Time Frame: Baseline through End of Study (up to 7.5 years)
    Safety Issue?: No
• Model Adjusted Change From Baseline in HbA1c at Month 60
  • Time Frame: Baseline and Month 60 of randomised dual therapy treatment period
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• Model Adjusted Change From Baseline in Body Weight at Month 60
  • Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase
    Safety Issue?: No
• Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60
  • Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase
    Safety Issue?: No
• Model Adjusted Change From Baseline in Waist Circumference at Month 60
  • Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• Model Adjusted Change From Baseline in Fibrinogen at Month 60
  • Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase
    Safety Issue?: No
• 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
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: GlaxoSmithKline Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00379769

Study ID Number: BRL-049653/231

ClinicalTrials.gov Identifier: NCT00379769

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency