IDNT, the Irbesartan Diabetic Nephropathy Trial compared an ARB to a CCB and placebo in DMII patients with CKD and proteinuria.
1715 patients were randomized from multiple centers around the world.
To be included in the study patients needed to be between 30-70 years old, have DMII and HTN (greater than 135/85), proteinuria (at least 900mg/24 hours), Cr 1.0-3.0 mg/dl in women and 1.2-3.0 mg/dl in men.
The study drug Irbesartan was started at 75mg and titrated to 300mg while Amlodipine was started at 2.5mg and titrated to 10mg per day.
The primary endpoint was doubling of serum Cr, ESRD (dialysis, transplantation or a Cr of 6.0 mg/dl) or death.
The secondary endpoint was a composite of death from cardiovascular causes, nonfatal MI, CHF resulting in hospitalization, a permanent neurologic deficit caused by a cerebrovascular event, or lower limb amputation above the ankle.
Mean followup time was 2.6 years.
Apart from there being slightly more men in the placebo group baseline characteristics were similar.
The ACRs were higher than in RENAAL with median values of 1.9 g/24hrs. An interesting little tidbit was that 24 hr urinary albumin was roughly 2/3rds that of total 24 hr urinary protein (did not know that).
Crs were around 1.7 mg/dl lower than the 1.9 mg/dl in RENAAL. Using demographic data MDRD eGFRs were approximately 44 ml/min/1.73m2 for men.
Blood pressures were also higher in IDNT than RENAAL with rough mean values of 160/87 vs 152/82 respectively.
During treatment the MAP was significantly higher (3.3 mmHg) in the placebo group when compared to the ARB and CCB groups (which were similar in MAP control).
The primary composite endpoint showed a statistically significant ARR of 6.4% and 8.5% and RR reduction of 20% and 23% when ARB was compared to placebo and amlodipine respectively. According to the authors adjustment for difference in BP did not alter these results.
The breakdown of the composite was as follows...
ARB reduced the risk of doubling of serum Cr when compared with both CCB and placebo. There were no statistically significant differences in ESRD or death from any cause between the groups.
Again impressive was overall just how at risk diabetics with CKD and significant proteinuria are with 22% doubling their Cr, 17% reaching ESRD and 15% dying over just 2.6 years.
The secondary outcome did not differ significantly between groups.
Proteinuria was on average reduced by 33% in the ARB group and the rate of decline in eGFR was 5.5 ml/min/1.73m2 vs 6.8 ml/min/1.73m2 and 6.5 ml/min/1.73m2 in the CCB and placebo groups respectively.
So nutshell...
Big international muticenter ARB vs CCB vs placebo trial with intention to treat analysis of diabetic nephropathy with macroalbuminuria showing reduction in the ARB group in the combined endpoint of mortality, ESRD or doubling of serum Cr driven by the reduction in doubling serum Cr.
Very similar to RENAAL with the added information that ARB is superior to amlodipine in this population.
Graham, hey I help run the renal fellow network now. Nathan was a huge inspiration for me as well send me an email at matthew.sparks@duke.edu would love to talk.
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