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Irbesartan Diabetic Nephropathy Trial - IDNT
Description:
The Irbesartan Diabetic Nephropathy Trial (IDNT) was a randomized, blinded, placebo-controlled trial designed to assess whether irbesartan or amlodipine slow the progression of nephropathy in patients with type 2 diabetes, independent of effects on systemic blood pressure (BP) lowering.
Hypothesis:
Treatment with irbesartan compared to placebo or treatment with amlodipine would result in a lower incidence of the composite endpoint of: doubling of serum creatinine, onset of end-stage renal disease, serum creatinine ≥6.0 mg/dl, or death from any cause.
Study Design
Study Design:
Patients Enrolled: 1,715
Mean Follow Up: 2.6 years
Mean Patient Age: 30-70
Female: 33%
Patient Populations:
Age between 30 and 70, a documented diagnosis of type 2 diabetes mellitus, hypertension (systolic BP >135 mm Hg while sitting, diastolic BP >85 mm Hg while sitting, or documented treatment with antihypertensive agents), and proteinuria, with urinary protein excretion of at least 900 mg per 24 hours. Serum creatinine was required to be 1.0–3.0 mg/dl (88–265 µmol/l) in women and 1.2–3.0 mg/dl (106–265 µmol/l) in men.
Exclusions:
Serum creatinine above 3.0 mg/dl
Primary Endpoints:
Composite of: doubling of serum creatinine, onset of end-stage renal disease, serum creatinine ≥6.0 mg/dl, or death from any cause
Secondary Endpoints:
1) Composite of: death from cardiovascular causes, nonfatal myocardial infarction, heart failure resulting in hospitalization, a permanent neurologic deficit caused by a cerebrovascular event, or lower limb amputation above the ankle.
2) Rate of increase in serum creatinine, mean change in serum creatinine, or mean rate of change in creatinine clearance.
Drug/Procedures Used:
Irbesartan titrated to 75-300 mg/day, amlodipine titrated 2.5-10 mg/day, or placebo
Concomitant Medications:
Standard care with targeted BP of 135/85 mm Hg (or less or 10 mm Hg lower than the value obtained at screening of systolic BP was >145 mm Hg); no additional or previous ACE inhibitors, angiotensin receptor blockers (ARBs), or calcium channel blockers were allowed.
Principal Findings:
A total of 1,715 diabetic patients with proteinuria and mild renal insufficiency (mean serum creatinine 1.67 mg/dl) were enrolled. The baseline characteristics of the groups were similar, with slightly less women in the placebo group, and higher mean arterial pressures in the placebo group.
The unadjusted relative risk of achieving the primary endpoint was 20% lower in the irbesartan group compared to placebo (32.6% vs. 39.0%, p=0.02) and was 23% lower than in the amlodipine group (32.6% vs. 41.1%, p=0.006). In addition, irbesartan slowed the rate of doubling of serum creatinine compared to amlodipine (by 21%, p=0.02) and placebo (by 24%, p=0.008).
There were no significant differences in renal outcomes between the amlodipine and placebo groups. In an adjusted analysis correcting for differences in baseline covariates such as BP, the relative risk of the primary endpoint was 0.81 in the irbesartan group versus placebo (p=0.03), 1.07 for amlodipine versus placebo (p=0.47), and 0.76 for irbesartan versus amlodipine (p=0.005).
No significant differences were seen in secondary cardiovascular endpoints between groups, and hyperkalemia necessitating a discontinuation of study medication was seen more often in the irbesartan group.
Interpretation:
Among patients with type 2 diabetes, the ARB irbesartan demonstrated a significantly decreased incidence of endpoints assessing the progression of renal disease compared to amlodipine and to placebo. These effects appeared to be independent of irbesartan’s effects in lowering BP.
References:
Lewis EJ, Hunsicker LG, Clarke WR, et al., for the Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60.
Keywords: Risk, Kidney Failure, Chronic, Arterial Pressure, Diabetes Mellitus, Type 2, Hyperkalemia, Proteinuria, Diabetic Nephropathies, Creatinine, Tetrazoles, Calcium Channel Blockers, Biphenyl Compounds, Angiotensin II Type 1 Receptor Blockers, Amlodipine, Hypertension
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