Preventing Microalbuminuria in Type 2 Diabetes

• Status: Completed
• Trial end date: 2016-09-01
• Target enrollment: 0
• Participant gender: All

Summary

In people with type 2 diabetes, microalbuminuria is a strong, independent risk factor for diabetic nephropathy and cardiovascular morbidity and mortality. ACE inhibitor therapy decreased the risk of microalbuminuria in hypertensive subjects with type 2 diabetes and normoalbuminuria by about 40%. Available data suggest that angiotensin II receptor blockers (ARBs) might have a similar renoprotective effect and that this effect might be increased by combined ACE inhibitor therapy.

The study will evaluate the effects, at similar blood pressure control (systolic/diastolic <130/80 mmHg), for a period of three years, of dual renin-angiotensin-system (RAS) blockade by benazepril and valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan alone on microalbuminuria and cardiovascular events in high-risk patients with type 2 diabetes, creatinine <1.5 mg/dl, no evidence of microalbuminuria but at high risk of renal disease, with hypertension and a urinary albumin excretion between 7 and 19 microgram/min. The relationship between albuminuria and cardiovascular outcomes will also be evaluated.

The study is expected to show a more effective prevention of microalbuminuria and cardiovascular events with combined than with single drug ACE inhibitor or ARB therapy. As compared to ACE inhibitor, ARB therapy is expected to have a similar effect on microalbuminuria, but an inferior cardioprotective effect. Applied to clinical practice, the findings should help preventing 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);

• History of diabetes not exceeding 25 years;

• High blood pressure (systolic and/or diastolic blood pressure >135/85 mmHg or concomitant treatment with blood pressure lowering medications);

• Serum creatinine concentration <1.5 mg/dl;

• Overnight urinary albumin excretion (in at least 2 of 3 consecutive overnight urine collections) ≥ 7 and <20 µg/min;

• Legal capacity;

• Written informed consent.

Exclusion Criteria:

• Uncontrolled diabetes (glycated hemoglobin >11%);

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

• Serum potassium ≥ 5.5 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.