A clinical trial in type 2 diabetic nephropathy

A prospective, randomized, three-armed, double-blind, placebo-controlled cl inical trial has been completed in 210 sites worldwide to determine whether the angiotensin If receptor blocker irbesartan or the calcium channel bloc ker amiodipine has a renoprotective effect in patients with overt type 2 di abetic nephropathy. A total of 1,715 subjects randomized during a 3-year pe riod were followed a minimum of 2 years. The goal for all treatment groups was to achieve equivalent blood pressure control, with the blinded study dr ug (irbesartan, amlodipine, or placebo) as primary therapy with additional anti hypertensive drugs, excluding angiotensin-converting enzyme inhibitors , calcium antagonists, and angiotensin II receptor antagonists, to achieve seated systolic blood pressure less than 135 mm Hg and diastolic blood pres sure less than 85 mm Hg. The primary outcome was the combined endpoint of t ime to doubling of entry serum creatinine, end-stage renal disease, or deat h. Secondary outcomes included fatal and nonfatal cardiovascular events. A Clinical Management Committee monitored the conduct of the study. An Outcom e Confirmation Committee classified all study outcome events in blinded fas hion. An external Data Safety Monitoring Committee monitored unblinded data for interim safety and efficacy analyses of the study. Eligibility criteri a included informed consent, age 30 to 70 years, adult-onset diabetes, hype rtension, urine protein excretion greater than 900 mg/24 hours, and serum c reatinine values of 90 to 265 mu mol/L in women and 110 to 265 mu mol/L in men. Baseline characteristics were age, 59 +/- 8 years; body mass index, 31 +/- 7 kg/m(2); 67% male; 73% white, 14% black, and 13% other; duration of diabetes, 15 +/- 9 years; retinopathy, 66%; neuropathy, 48%; congestive hea rt failure, 7.5%; screening seated systolic blood pressure, 156 +/- 18 mm H g, and diastolic blood pressure, 86 +/- 11 mm Hg; urine protein excretion, 4.0 +/- 3.5 g/24 hours; serum creatinine, 150 +/- 53 mu mol/L; serum potass ium, 4.6 +/- 0.5 mEq/L; total cholesterol, 229 +/- 58 mg/dL; and hemoglobin A(1c), 8.1 +/- 1.7%. This large-scale international trial should help defi ne the clinical course and standards of care for hypertensive adults with t ype 2 diabetes mellitus and nephropathy. Results available on May 19, 2001, will help in defining the current controversy of the risks and benefits of blockade of the renin-anglotensin system versus calcium channel blockade v ersus standard antihypertensive therapy in this large patient population. ( C) 2001 by the National Kidney Foundation, Inc.