Angiotensin-converting-enzyme (ACE) Inhibitors in Hemodialysis
Status:
Completed
Trial end date:
2016-04-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research