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Angiotensin-converting-enzyme (ACE) Inhibitors in Hemodialysis (ARCADIA)

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ClinicalTrials.gov Identifier: NCT00985322
Recruitment Status : Completed
First Posted : September 28, 2009
Last Update Posted : June 1, 2016
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief 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 624 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.


Condition or disease Intervention/treatment Phase
Left Ventricular Hypertrophy Hypertension Drug: ACE inhibitor Ramipril Drug: non-RAS inhibitor antihypertensive therapy Phase 3

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Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 269 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open Label, Blinded End-point (Probe) Trial to Evaluate Whether, at Comparable Blood Pressure Control, ACE Inhibitor Therapy More Effectively Than Non RAS Inhibitor Therapy Reduces CArdiovascular Morbidity and Mortality in Chronic DIAlysis Patients With Left Ventricular Hypertrophy and/or Arterial Hypertension (ARCADIA Study)
Study Start Date : May 2009
Primary Completion Date : April 2016
Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Ramipril
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: ACE inhibitor Ramipril 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.
Active Comparator: non-RAS inhibitor antihypertensive therapy Drug: non-RAS inhibitor antihypertensive therapy
Blood Pressure lowering regimen not including RAS inhibitors


Outcome Measures

Primary Outcome Measures :
  1. The main outcome variable will be a combined end-point of cardiovascular death (including sudden death and cardiac arrest resuscitation) and myocardial infarction or non-fatal stroke. [ Time Frame: Baseline, 1st and 2nd year ]

Secondary Outcome Measures :
  1. Single components of combined endpoint,myocardial or peripheral revascularizations,new onset paroxysmal,persistent or permanent or recurrence of atrial fibrillation,hospitalizations for chronic heart failure,and thrombosis of artero-venous fistula [ Time Frame: Baseline, 1st and 2nd year ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Men and women >18 years of age who are on chronic renal replacement treatment since at least 6 months with two or three haemodialysis sessions per week.
  • Hypertension (pre-dialysis systolic and/or diastolic BP >140/90 mmHg or post-dialysis systolic and/or diastolic BP >130/80 mmHg or ongoing antihypertensive therapy).

and/or

  • LVH defined by a cardiac mass index >130 g/m2 for men and 100 g/m2 for women (17) within three months of enrolment.
  • Written informed consent.

Exclusion criteria:

  • Specific indication (such as heart failure) or contraindication (such as hypersensitivity) to ACE inhibitor therapy.
  • Any concomitant medication with ACE inhibitors and angiotensin II receptor antagonists
  • Hyperkalemia (serum potassium >6 mEq/L) despite optimal control of metabolic acidosis and blood glucose (in diabetics) in patient with less then three dialysis sessions per week.
  • Symptomatic chronic or intradialytic hypotension.
  • Arrhythmias that in the Investigator judgement might be worsened by hyperkalemia (such as sinus bradycardia, delayed atrio-ventricular conduction, atrio-ventricular blocks).
  • CV events (stroke, acute myocardial infarction or other acute coronary syndromes) over the last three months.
  • Uncontrolled hyper- or hypo-thyroidism.
  • Active systemic disease, malignancies and any clinical condition associated with a life-expectancy of less than 2 years.
  • Drug or alcohol abuse, psychiatric disorders and inability to understand the potential risks or benefits of the study.
  • Pregnancy, lactation or child bearing potential and ineffective contraception.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00985322


Locations
Italy
Policlinico San Pietro
Ponte San Pietro, Bergamo, Italy
Ospedale "Treviglio-Caravaggio"
Treviglio, Bergamo, Italy
Hospital of Montichiari
Montichiari, Brescia, Italy
Presidio Ospedaliero Acireale
Acireale, Catania, Italy
Hospital "Morgagni-Pierantoni"
Forlì, Forlì Cesena, Italy
A.O. Desio e Vimercate
Desio, MB, Italy
Ospedale "Caduti Bollatesi"
Bollate, Milano, Italy
Hospital of Cernusco sul Naviglio
Cernusco sul Naviglio, Milano, Italy
Hospital "Bassini"
Cinisello Balsamo, Milano, Italy
A.O. Ospedale Civile di Legnano
Legnano, Milano, Italy
A.O. della Provincia di Lodi
Lodi, Milano, Italy
Presidio Ospedaliero di Magenta
Magenta, Milano, Italy
IRCCS "Humanitas"
Rozzano, Milano, Italy
IRCCS Multimedia
Sesto San Giovanni, Milano, Italy
Fondazione San Raffaele Monte Tabor
Milan, MI, Italy
Ospedale San Giovanni di Dio
Agrigento, Italy
Cliniche Humanitas Gavazzeni
Bergamo, Italy
Hospital "Ospedali Riuniti "
Bergamo, Italy
Hospital "Policlinico S.Orsola-Malpighi"
Bologna, Italy
A.O. Giuseppe Brotzu
Cagliari, Italy
ASL 8 - S.C. Territoriale di Nefrologia e Dialisi
Cagliari, Italy
A.O. S. Croce e Carle, Cuneo
Cuneo, Italy
Hospital "San Paolo"
Milano, Italy
Hospital "San Gerardo"
Monza, Italy
Hospital "Azienda Ospedaliera Universitaria Di Parma"
Parma, Italy
Arcispedale Santa Maria Nuova
Reggio Emilia, Italy
Hospital "Degli Infermi"
Rimini, Italy
A.O. Umberto I
Siracusa, Italy
P.O. G. Mazzini
Teramo, Italy
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Agenzia Italiana del Farmaco
Investigators
Study Director: Piero Ruggenenti, MD Mario Negri Institute for Pharmacological Research
More Information

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT00985322     History of Changes
Other Study ID Numbers: ARCADIA
2008-003529-17 ( EudraCT Number )
First Posted: September 28, 2009    Key Record Dates
Last Update Posted: June 1, 2016
Last Verified: May 2016

Keywords provided by Mario Negri Institute for Pharmacological Research:
Hemodialysis

Additional relevant MeSH terms:
Hypertension
Hypertrophy
Hypertrophy, Left Ventricular
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Cardiomegaly
Heart Diseases
Antihypertensive Agents
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action