Preventing ESRD in Overt Nephropathy of Type 2 Diabetes

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.

Conditions

• Diabetes

Interventions

DRUG

Benazepril

Patients satisfying the inclusion/exclusion criteria will be randomly given equivalent doses (half the standard doses recommended by the manufacturer for blood pressure control) of benazepril (10 mg/day) or valsartan (160 mg/day) or one fourth of the standard doses of both agents in combination (benazepril 5 mg/day and valsartan 80 mg/day).If well tolerated, treatment will be up-titrated to full dose of benazepril (20 mg/day) or valsartan (320 mg/day) or one half of the standard doses of both agents in combination (benazepril 10 mg/day and valsartan 160 mg/day).

DRUG

Valsartan

Patients satisfying the inclusion/exclusion criteria will be randomly given equivalent doses (half the standard doses recommended by the manufacturer for blood pressure control) of benazepril (10 mg/day) or valsartan (160 mg/day) or one fourth of the standard doses of both agents in combination (benazepril 5 mg/day and valsartan 80 mg/day).If well tolerated, treatment will be up-titrated to full dose of benazepril (20 mg/day) or valsartan (320 mg/day) or one half of the standard doses of both agents in combination (benazepril 10 mg/day and valsartan 160 mg/day).

DRUG

Benazepril/Valsartan

Patients satisfying the inclusion/exclusion criteria will be randomly given equivalent doses (half the standard doses recommended by the manufacturer for blood pressure control) of benazepril (10 mg/day) or valsartan (160 mg/day) or one fourth of the standard doses of both agents in combination (benazepril 5 mg/day and valsartan 80 mg/day).If well tolerated, treatment will be up-titrated to full dose of benazepril (20 mg/day) or valsartan (320 mg/day) or one half of the standard doses of both agents in combination (benazepril 10 mg/day and valsartan 160 mg/day).

Sponsors & Collaborators

• Agenzia Italiana del Farmaco

  collaborator OTHER_GOV

• Mario Negri Institute for Pharmacological Research

  lead OTHER

Principal Investigators

• Giuseppe Remuzzi, MD · Mario Negri Institute for Pharmacological Research

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-05-31

Primary Completion

2016-04-30

Completion

2016-04-30

Countries

• Italy
• Slovenia

Study Locations