Angiotensin-converting-enzyme (ACE) Inhibitors in Hemodialysis

Summary

Background: Angiotensin-converting-enzyme (ACE) inhibitors have a specific cardioprotective effect and, compared to treatment not directly interfering with the renin-angiotensin-system (RAS), significantly reduce cardiovascular (CV) mortality and morbidity in subjects with normal renal function.

Despite CV events are the leading cause of death in these patients, no adequately powered trial so far evaluated the specific cardioprotective effect of ACE inhibitors in this population.

Objectives: This prospective, randomized, open label, blinded end point (PROBE) trial is primarily aimed at evaluating whether, at comparable blood pressure (BP) control, ACE inhibitor as compared to non-RAS inhibitor therapy significantly reduces the incidence of a composite end point of CV death (including sudden death) and non-fatal myocardial infarction or stroke in 266 patients with arterial hypertension (pre-dialysis systolic/diastolic BP \>140/90 mmHg or post-dialysis systolic/diastolic BP \>130/80 mmHg or antihypertensive therapy) and/or echocardiography evidence of LVH (cardiac mass index \>130 g/m2 for men and 100 g/m2 for women) who are on dialysis therapy since at least six months. Secondarily, the study will compare the incidence of single components of the primary outcome, new onset paroxysmal or persistent atrial fibrillation, thrombosis of the artero-venous fistula, new onset, progression or regression of LVH, changes in components of the metabolic syndrome, the safety profile of the two treatment regimens and their cost/effectiveness.

Methods: After 1 month wash-out period from previous RAS inhibitor therapy and a baseline evaluation of main clinical and laboratory parameters, patients will be randomized on a 1:1 basis to 2-year treatment with an ACE inhibitor or a BP lowering regiment not including RAS inhibitors. A balanced distribution according to centre, number of dialysis sessions per week (2 or 3), presence of diabetes (YES/NO), arterial hypertension (YES/NO), LVH (YES/NO) will be achieved by the minimization method. Treatment will be adjusted to achieve and maintain a target BP \<140/90 mmHg (pre-dialysis) and a target BP \<130/80 mmHg (post-dialysis) in both groups.

Expected results: ACE inhibitor compared to non-RAS inhibitor therapy is expected to reduce more effectively fatal and non-fatal CV events, prevent or limit progression or induce regression of LVH, improve some components of the metabolic syndrome, and reduce treatment costs for cardiovascular complications. These findings might help achieving more effective cardioprotection in people on chronic dialysis at lower costs.

Conditions

• Left Ventricular Hypertrophy
• Hypertension

Interventions

DRUG

ACE inhibitor Ramipril

The ACE inhibitor (Ramipril) will be started at 1.25 mg/day and will be up-titrated to 2.5 mg/day, to 5 mg/day, and then to 10 mg/day according to BP control and tolerability.

DRUG

non-RAS inhibitor antihypertensive therapy

Blood Pressure lowering regimen not including RAS inhibitors

Sponsors & Collaborators

• Agenzia Italiana del Farmaco

  collaborator OTHER_GOV

• Mario Negri Institute for Pharmacological Research

  lead OTHER

Principal Investigators

• Piero Ruggenenti, MD · Mario Negri Institute for Pharmacological Research

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-05-31

Primary Completion

2016-04-30

Completion

2016-04-30

Countries

• Italy

Study Locations