The Irbesartan in Diabetic Nephropathy Trial

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The Irbesartan in Diabetic Nephropathy Trial

• IDNT overview
• Randomized, double-blind trial to determine if
  irbesartan, an angiotensin II receptor blocker,
  and amlodipine, a calcium channel blocker, slow
  the progression of nephropathy in type 2
  diabetics
• Population
• 1,715 patients (30 to 70 years old)
• Diagnosed type 2 diabetes
• Hypertension (systolic BPgt135, diastolic BP gt85
  mmHg or treatment w/ antihypertensive agents)
• Nephropathy (urinary protein excretion of at
  least 900 mg/24hrs and serum creatinine between
  1.03.0 mg/dL in women, and 1.23.0 mg/dL in men)

www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
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IDNT Study Design
Irbesartan 300 mg/qd n579
Target Blood Pressure 135/ 85 mmHg
Potential participants discontinue ACEIs, ARBs
and CCBs at least 10 days prior to screening
1,715 patients randomized and followed
Amlodipine 10 mg/qd n567
Placebo n569
(or 10 mmHg lower than the value at screening if
it was more than 145 mmHg)
Average follow-up of 2.6 years
Screening phase of up to 5 weeks
www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
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IDNT Endpoints

• Primary Endpoint
• Composite of a doubling of serum creatinine, end
  stage renal disease (as indicated by starting
  dialysis, serum creatinine ? 6 mg/dl, or
  transplantation), or death
• Secondary Cardiovascular Endpoint
• 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

www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
4
IDNT Baseline Characteristics
The differences between the treatment groups
were not statistically significant, except for
the smaller number of females in the placebo
group (P0.02)
www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
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IDNT Irbesartan vs Amlodipine Primary and
Secondary Endpoints
Composite of a doubling of serum creatinine, end
stage renal disease, or death 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
www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
6
IDNT Irbesartan vs Placebo Primary and Secondary
Endpoints
Composite of a doubling of serum creatinine, end
stage renal disease, or death 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
www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
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IDNT Summary of Important Findings

• In hypertensive, type 2 diabetics with
  nephropathy
• Irbesartan reduced the incidence of the primary
  composite endpoint of a doubling of serum
  creatinine, end stage renal disease, or death by
  23 vs amlodipine (P0.006) and 20 vs placebo
  (P0.02)
• Proteinuria was reduced 33 in the irbesartan
  group compared to 10 with placebo
• These benefits were above and beyond those
  attributable to blood pressure reduction alone

www.hypertensiononline.org
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.