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

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety Study
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:

MedlinePlus related topics: Diabetes

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 ]

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 ]
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 ]
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 ]
Number of Participants With CV/Microvascular Events [ Time Frame: Baseline through End of Study (up to 7.5 years) ] [ Designated as safety issue: No ]
Number of Participants With Glycaemic Failure Events [ Time Frame: Baseline through to end of randomised dual therapy ] [ Designated as 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) ] [ Designated as 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) ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

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
add-on medication: Active Comparator 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 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 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: 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 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.

Arms

Assigned Interventions

add-on medication: Active Comparator

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 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 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: 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 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.

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

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

Show 458 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Komajda M, Curtis P, Hanefeld M, Beck-Nielsen H, Pocock SJ, Zambanini A, Jones NP, Gomis R, Home PD; RECORD Study Group. Effect of the addition of rosiglitazone to metformin or sulfonylureas versus metformin/sulfonylurea combination therapy on ambulatory blood pressure in people with type 2 diabetes: a randomized controlled trial (the RECORD study). Cardiovasc Diabetol. 2008 Apr 24;7:10.

Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ; RECORD Study Group. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. N Engl J Med. 2007 Jul 5;357(1):28-38. Epub 2007 Jun 5.

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	BRL-049653/231
Study First Received:	September 21, 2006
Results First Received:	August 24, 2009
Last Updated:	January 28, 2010
ClinicalTrials.gov Identifier:	NCT00379769 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:

diabetes
rosiglitazone
metformin
sulfonylurea

Additional relevant MeSH terms:

Hypoglycemic Agents
Metabolic Diseases
Physiological Effects of Drugs
Metformin
Diabetes Mellitus, Type 2

Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Rosiglitazone
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 08, 2010