Preventing ESRD in Overt Nephropathy of Type 2 Diabetes

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborator: Agenzia Italiana del Farmaco
• Treatments: Benazepril; Valsartan

Criteria

Inclusion Criteria:

• Males and females >40 years old;

• High-risk subjects with type 2 diabetes (WHO criteria);

• Serum creatinine concentration of 1.8 mg/dl or more (but less than 3.5 mg/dl);

• Urinary 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 (in spot morning urine)

• Legal capacity;

• Written informed consent.

Exclusion Criteria:

• Specific contraindications or history of hypersensitivity to the study drugs or other;

• Serum potassium ≥ 6 mEq/L despite diuretic therapy, and optimized metabolic and acid/base control;

• Bilateral renal artery stenosis;

• Previous history of allergy or intolerance, or evidence of immunologically-mediated renal disease, systemic diseases, cancer;

• Drug or alcohol abuse;

• Any chronic clinical conditions that may affect completion of the trial or confound data interpretation;

• Pregnancy or lactating;

• Women of childbearing potential without following a scientifically accepted form of contraception;

• Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequence of the trial;

• Evidence of an uncooperative attitude;

• Any evidence that patient will not be able to complete the trial follow-up;

• Dual RAS blockade with an ACE inhibitor and an ARB.