The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)

Completed · Phase 3 · Has a placebo group

Conditions studied: Diabetes Mellitus, Non-Insulin-Dependent

In brief

The primary objectives of the ORIGIN study were: * To determine whether insulin glargine-mediated normoglycemia can reduce cardiovascular morbidity and/or mortality in people at high risk for vascular disease with either Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or early type 2 diabetes; * To determine whether omega-3 fatty acids can reduce cardiovascular mortality in people with IFG, IGT or early type 2 diabetes. The secondary objectives of the insulin glargine study were to determine if insulin glargine-mediated normoglycemia can reduce: * total mortality (all causes); * the risk of diabetic microvascular outcomes; * the rate of progression of IGT or IFG to type 2 diabetes.

Key facts

Study ID

NCT00069784

Run by

Sanofi

People needed

12537

Starts

2003-08-01

Expected to finish

2011-12-01

Last updated by the study team

2013-01-31

Who can join

Age: 50 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• I1. Individuals with IFG and/or IGT, or early diabetes, as defined below.
• Glucose tolerance status was determined by a 75 g oral glucose tolerance test (OGTT) that was performed fasting (ie, no consumption of food or beverage other than water for at least 8 hours) at the time of screening for all candidates who were not known to have diabetes. The qualifying OGTT could be obtained up to 4 weeks prior to screening provided that anti-diabetic therapy (if any) remained unchanged between the qualifying OGTT and the screening visit. Two plasma glucose values were drawn during the OGTT - a fasting value (FPG) and a value drawn two hours after the 75 g oral glucose load was administered (postprandial plasma glucose [PPG]).
• Impaired glucose tolerance (IGT), defined as a PPG value ≥140 and <200 mg/dL (ie, ≥7.8 and <11.1 mmol/L), with a FPG <126 mg/dL (7.0 mmol/L).
• OR
• Impaired fasting glucose (IFG), defined as an FPG ≥110 and <126 mg/dL (≥6.1 and <7 mmol/L), without diabetes mellitus (PPG must be <200 mg/dL [11.1 mmol/L]).
• OR
• Early type 2 diabetes, defined as a FPG ≥126 mg/dL (7.0 mmol/L) or a PPG of ≥200 mg/dL (11.1 mmol/L), or a previous diagnosis of diabetes, and either:
• on no pharmacological treatment (while ambulatory) for at least 10 weeks prior to screening, with screening glycated hemoglobin <150% of the upper limit of normal (ULN) for the laboratory (eg, <9% if the ULN is 6%)
• or taking one oral antidiabetic drug (OAD) from among sulfonylureas (SU), biguanides, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), and meglitinides (MGTs) at a stable dose while ambulatory for at least 10 weeks at the time of screening (or for the 10 weeks prior to hospitalization if identified while hospitalized for a CV event), with screening glycated hemoglobin <133% of the ULN for the laboratory (eg, <8% if the ULN is 6%) if taking this medication at half-maximum dose or greater, and glycated hemoglobin <142% of the ULN for the laboratory (eg, <8.5% if the ULN is 6%) if taking this medication at less than half-maximum dose. Individuals taking combination products containing two or more OADs were not eligible.
• I2. Men or women aged 50 years and older
• I3. At least one of the following CV risk factors:
• previous myocardial infarction (MI) (≥ 5 days prior to randomization)
• previous stroke (≥ 5 days prior to randomization)
• previous coronary, carotid or peripheral arterial revascularization
• angina with documented ischemic changes (at least 2 mm ST segment depression on electrocardiogram during a Graded Exercise Test [GXT]; or with a cardiac imaging study positive for ischemia); or unstable angina with documented ischemic changes (either ST segment depression of at least 1 mm or an increase in troponin above the normal range but below the range diagnostic for acute myocardial infarction)
• microalbuminuria or clinical albuminuria (an albumin: creatinine ratio ≥ 30 μg/mg in at least one or timed collection of urine with albumin excretion ≥20 μg/min or ≥30 mg/24 hours or total protein excretion ≥500 mg/24 hours)
• left ventricular hypertrophy by electrocardiogram or echocardiogram
• significant stenosis on angiography of coronary, carotid, or lower extremity arteries (ie, 50% or more stenosis)
• ankle-brachial index < 0.9.
• I4. Provision of signed and dated informed consent prior to any study procedures.
• I5. Ability and willingness to complete study diaries and questionnaires.
• I6. Demonstrated ability to use the self-glucose-monitoring device, and to self-inject insulin prior to randomization.
• I7. A negative pregnancy test for all women of childbearing potential (ie, ovulating, pre- menopausal, and not surgically sterile) and the agreement of these women to use a reliable method of birth control to prevent pregnancy during the duration of the study .
• I8. Willingness to discontinue prior omega-3 PUFA supplements for the duration of the study.

You may not qualify if…

• E1. Type 1 diabetes.
• E2. Requiring ambulatory insulin treatment or uncontrolled or symptomatic hyperglycemia that is likely to require the addition of ambulatory insulin therapy or a new antidiabetic agent either before or within 2 weeks after randomization.
• E3. Known anti-glutamic acid decarboxylase antibody (anti-GAD Ab) positivity in the past.
• E4. Screening glycated hemoglobin ≥150% of the ULN for the laboratory (eg, ≥9% if the ULN is 6%).
• E5. Unwillingness to inject insulin or perform self-monitoring of blood glucose.
• E6. Nonadherence to the run-in requirement to inject placebo insulin and do capillary glucose monitoring for at least 4 days prior to randomization.
• E7. Coronary artery bypass grafting (CABG) either planned at the time of screening, or CABG within the 4 years prior to screening - however, participants with angina, MI, or stroke since a previous CABG will be eligible for randomization, even if the last CABG was within 4 years.
• E8. Serum creatinine >2.0 mg/dL (176 μmol/L) at screening.
• E9. Active liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times ULN at screening.
• E10. Chronic or recurrent treatment with systemic corticosteroids, or niacin treatment for hyperlipidemia.
• E11. Heart failure of New York Heart Association (NYHA) Functional Class III or IV.
• E12. Expected survival of <3 years for non-CV causes such as cancer.
• E13. Any other factor likely to limit protocol compliance or reporting of adverse events (AEs).
• E14. Unwilling or unable to discontinue TZDs.
• E15. Simultaneous participation in any other clinical trial of an active pharmacologic agent.
• E16. Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data and treatment assignment.
• E17. History of hypersensitivity to the investigational products.
• E18. Previous randomization in this study.
• E19. A prior heart transplant, or awaiting a heart transplant.
• E20. Known infection with human immunodeficiency virus (HIV).

Where it is running

• Sanofi-Aventis Administrative Office — Bridgewater, New Jersey, United States
• Sanofi-Aventis Administrative Office — Buenos Aires, Argentina
• Sanofi-Aventis Administrative Office — Cove, New South Wales, Australia
• Sanofi-Aventis Administrative Office — Vienna, Austria
• Sanofi-Aventis Administrative Office — Minsk, Belarus
• Sanofi-Aventis Administrative Office — Hamilton, Bermuda
• Sanofi-Aventis Administrative Office — São Paulo, Brazil
• Sanofi-Aventis Administrative Office — Laval, Quebec, Canada
• Sanofi-Aventis Administrative Office — Santiago, Chile
• Sanofi-Aventis Administrative Office — Beijing, China
• Sanofi-Aventis Administrative Office — Cali, Colombia
• Sanofi-Aventis Administrative Office — Zagreb, Croatia
• Sanofi-Aventis Administrative Office — Hørsholm, Denmark
• Sanofi-Aventis Administrative Office — Tatari, Estonia
• Sanofi-Aventis Administrative Office — Helsinki, Finland
• Sanofi-Aventis Administrative Office — Paris, France
• Sanofi-Aventis Administrative Office — Berlin, Germany
• Sanofi-Aventis Administrative Office — Budapest, Hungary
• Sanofi-Aventis Administrative Office — Mumbai, India
• Makati City — Dublin, Ireland
• Sanofi-Aventis Administrative Office — Netanya, Israel
• Sanofi-Aventis Administrative Office — Milan, Italy
• Sanofi-Aventis Administrative Office — Riga, Latvia
• Sanofi-Aventis Administrative Office — Vilnius, Lithuania
• Sanofi-Aventis Administrative Office — México, Mexico

Full record on ClinicalTrials.gov

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