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Irbesartan in Type 2 Diabetes With Microalbuminuria 2 - IRMA 2
Description:
The Irbesartan in Type 2 Diabetes With Microalbuminuria 2 (IRMA 2) was a prospective, randomized, placebo-controlled, multicenter study designed to evaluate the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria.
Hypothesis:
Irbesartan is effective in delaying or preventing the development of diabetic nephropathy in hypertensive patients with type 2 diabetes and persistent microalbuminuria.
Study Design
Study Design:
Patients Screened: 1,469
Patients Enrolled: 590
Mean Follow Up: Two years
Mean Patient Age: 30-70
Female: 33
Patient Populations:
The trial involved hypertensive patients, ranging in age from 30 to 70 years, with type 2 diabetes, persistent microalbuminuria (defined as an albumin excretion rate of 20-200 μg/min in two of three consecutive, sterile, overnight samples) and a serum creatinine concentration of no more than 1.5 mg/dl for men and 1.1 mg/dl for women.
Exclusions:
Nondiabetic kidney disease, cancer, life-threatening disease with death expected to occur within two years, and an indication for ACE inhibitors or angiotensin-II-receptor antagonists
Primary Endpoints:
Time from the baseline visit to the first detection of overt nephropathy, defined by a urinary albumin excretion rate in an overnight specimen that was greater than 200 μg/min and at least 30% higher than the baseline rate on at least two consecutive visits
Secondary Endpoints:
Changes in the level of microalbuminuria, changes in the creatinine clearance, and the restoration of normoalbuminuria (a urinary albumin excretion rate of less than 20 μg/min) by the time of the last visit
Drug/Procedures Used:
The patients were randomly assigned to receive irbesartan in a dose of 150 mg/day, irbesartan in a dose of 300 mg/day, or matching placebo. The dose of medication was increased to the target level in two stages lasting two weeks each. The patients were examined at the time of randomization, two and four weeks after randomization, and at 3, 6, 12, 18, and 22 to 24 months. A clinical examination, measurements of the blood pressure, the urinary albumin excretion, the serum creatinine concentration, the glycosylated hemoglobin concentration, and other laboratory evaluations were performed at each visit.
Concomitant Medications:
Patients continued to receive their usual care for diabetes. No restriction on dietary salt or protein was implemented. Additional antihypertensive drugs used by patients included diuretics, beta-blockers, calcium channel blockers (except dihydropyridines), and alpha-blockers; angiotensin-converting enzyme (ACE) inhibitors were not allowed.
Principal Findings:
A total of 590 randomized patients were followed for a median of two years. Baseline demographic, clinical, and biochemical characteristics were balanced among the three groups. During the 24-month study, nephropathy developed in 30 patients in the placebo group, as compared with 19 patients in the 150 mg group (p=0.08) and 10 patients in the 300 mg group (p<0.001).
After adjustment for the baseline level of microalbuminuria and the blood pressure achieved during the study, the hazard ratio for diabetic nephropathy was 0.56 in the 150 mg group (95% confidence interval [CI] 0.31-0.99; p=0.05) and 0.32 in the 300 mg group (05% CI 0.15-0.65; p<0.001). Irbesartan reduced the level of urinary albumin excretion throughout the study. In the 150 mg group it decreased by 24%, in the 300 mg group it decreased by 38%, whereas there was a 2% decrease in the placebo group (p<0.001 for the comparison between placebo and the combined irbesartan groups).
Interpretation:
Among hypertensive patients with type 2 diabetes and persistent microalbuminuria, treatment with irbesartan significantly reduces the rate of progression to clinical albuminuria, the hallmark of overt diabetic nephropathy. The renoprotective effect of irbesartan appears to be independent of the systemic blood pressure because the average trough blood pressure during the study was only minimally lower in the irbesartan groups than in the placebo group, with no difference in diastolic blood pressure and a difference of 1-3 mm Hg in systolic blood pressure.
References:
Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P, for the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-8.
Keywords: Glycated Hemoglobin A, Biphenyl Compounds, Diabetes Mellitus, Type 2, Blood Pressure, Confidence Intervals, Creatinine, Diabetic Nephropathies, Tetrazoles
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