Preventing ESRD in Overt Nephropathy of Type 2 Diabetes
Status:
Completed
Trial end date:
2016-04-01
Target enrollment:
Participant gender:
Summary
Nephropathy of type 2 diabetes is the leading cause of end stage renal disease (ESRD)
world-wide and is associated with a dramatic excess cardiovascular morbidity and mortality.
Two randomized trials found that angiotensin II receptor blockers (ARBs) reduce the incidence
of ESRD by about 30%, but have no appreciable effects on cardiovascular mortality. Available
data suggest that ACE inhibitors might be similarly renoprotective and even more
cardioprotective, but large scale trials on ACE inhibitors, alone or combined with ARBs, in
overt nephropathy of type 2 diabetes are missing.
This study will compare the effects, at comparable blood pressure control (systolic/diastolic
<130/80 mmHg), of dual renin-angiotensin-system (RAS) blockade by half dose of benazepril and
valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan
alone at full dose, 20 mg and 160 mg respectively, on ESRD and cardiovascular events in
high-risk patients with type 2 diabetes and overt nephropathy, defined as serum creatinine
>1.8 mg/dl and < 3.2 mg/dl and spot morning urine albumin to creatinine ratio >1000mg/g for
the patients without previous ACE inhibitor and ARB therapy and >500mg/g for the patients
with previous ACE inhibitor or ARB therapy and no specific contraindications to the study
drugs. The relationships between renal and cardiovascular outcomes will also be evaluated.
102 patients will be treated for at least 3 years. At comparable blood pressure control, the
study is expected to show a more effective reduction in ESRD and cardiovascular events with
combined than with single drug ACE inhibitor or ARB therapy. As compared to ARB, ACE
inhibitor therapy is expected to have a similar effect on ESRD, but a superior
cardioprotective effect. Applied to clinical practice, the findings should help reducing
renal and cardiovascular complications, and related treatment costs, of type 2 diabetes.
Phase:
Phase 3
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research