The DREAM (Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication) Trial

Cardiovascular Disease Clinical Trial

Official title:

The DREAM (Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095654
• Other study ID #: DREAM30Nov2002
• Status: Completed
• Phase: Phase 3
• First received: November 5, 2004
• Last updated: November 9, 2009
• Start date: July 2001
• Est. completion date: October 2006

Study information

• Verified date: November 2009
• Source: Gerstein, Hertzel, MD
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if ramipril and/or rosiglitazone prevent the onset of type 2 diabetes.

Description:

The DREAM trial is a large, international, multi-centre, randomized double-blind controlled trial. A total of at least 4000 participants with impaired glucose tolerance (IGT) and 1000 participants with isolated impaired fasting glucose (IIFG) will be recruited from major international centres over an 18 month period. They will be randomly allocated to either ramipril and/or rosiglitazone using a 2X2 factorial design and followed for at least 3 years after randomization. Participants will be assessed at regular intervals to ascertain the occurrence of the primary outcome (new onset diabetes mellitus or all cause mortality) and other secondary outcomes. A diagnosis of diabetes will be made if 2 consecutive plasma glucose levels exceed the diagnostic thresholds (i.e. a fasting plasma glucose >=7.0 mmol/l (126 mg/dl) or a 2 hr plasma glucose >=11.1 mmol/l (200 mg/dl)) within a 3 month period. Assuming an annual event rate of 5%, this sample size provides 90% power to detect a 22% reduction in the rate of the primary outcome.

Potential Significance of the Study: This study could provide new strategies for the prevention of type 2 diabetes as well as provide insight into the relationship between cardiovascular disease and diabetes.

Study Update: A total of 5269 participants were enrolled into the study. 4527 Participants had IGT and 739 participants had IIFG. The study is currently in the follow-up phase.

DREAM On

In order to determine whether or not the benefits observed during the active phase of the trial are sustained after cessation of active medication use, further follow-up of the DREAM cohort will be conducted in the passive DREAM ObservatioN (DREAM On) follow-up study.

DREAM On will assess approximately 1500 consenting DREAM participants without a diagnosis of diabetes at the end of the washout phase after a post-trial period of between 1 and 2 years to determine the effect of on-trial exposure to rosiglitazone and/or exposure to ramipril on: a) the primary outcome (incident diabetes or death); and b) regression or maintenance of normoglycemia. Participants will be free to take any medications that are indicated and may participate in other research studies, according to the judgment of their own physician.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5000
• Est. completion date: October 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• impaired glucose tolerance (FPG < 7 mmol/L or 126 mg/dL AND 2 hr PG >= 7.8 mmol/L and < 11.1 mmol/L (140 mg/dL and < 200 mg/dL)or,

• isolated impaired fasting glucose (FPG >= 6.1 mmol/L and < 7 mmol/L (FPG >= 95 mg/dL and < 126 mg/dL) AND 2 hr PG < 7.8 mmol/L (140 mg/dL).

Exclusion Criteria:

• current use of an ACE-inhibitor (ACE-I) or thiazolidinedione(TZD)

• known hypersensitivity to ACE-I

• prior use of anti-diabetic medications (with the exception of during pregnancy)

• use of systemic glucocorticoids or niacin

• congestive heart failure or EF < 40%

• existing cardiovascular disease (previous MI, stroke, angina, uncontrolled hypertension)

• diabetes

• renal or hepatic disease

• major illness

• use of another experimental drug

• pregnant or unwilling to use reliable contraception

• major psychiatric disorder

• diseases that affect glucose tolerance

• unwillingness to be randomized or sign informed consent

• known uncontrolled substance abuse

• inability to communicate with research staff

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Glucose Intolerance
• Glucose Metabolism Disorders
• Impaired Glucose Tolerance
• Metabolic Diseases

Intervention

Drug:
• Ramipril

• Rosiglitazone

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Gerstein, Hertzel, MD	Aventis Pharmaceuticals, Canadian Institutes of Health Research (CIHR), GlaxoSmithKline, King Pharmaceuticals is now a wholly owned subsidiary of Pfizer, Wyeth is now a wholly owned subsidiary of Pfizer

References & Publications (3)

DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators, Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman RR. Effect of rosiglit — View Citation

DREAM Trial Investigators, Bosch J, Yusuf S, Gerstein HC, Pogue J, Sheridan P, Dagenais G, Diaz R, Avezum A, Lanas F, Probstfield J, Fodor G, Holman RR. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006 Oct 12;355(15):1551-62. Epub 2006 — View Citation

Gerstein HC, Yusuf S, Holman R, Bosch J, Pogue J; DREAM Trial Investigators. Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia. 2004 Sep;47(9):1519-27. Epub 2004 Aug 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	diabetes
Primary	death
Secondary	Myocardial infarction (MI)
Secondary	Stroke
Secondary	Congestive Heart Failure
Secondary	Angina
Secondary	Revascularization procedures
Secondary	Ventricular Arrhythmia
Secondary	Renal Events