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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Agenzia Italiana del Farmaco
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT00985322
First received: September 25, 2009
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Left Ventricular Hypertrophy
Hypertension
Drug: ACE inhibitor Ramipril
Drug: non-RAS inhibitor antihypertensive therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 269
Study Start Date: May 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Hospital "Ospedali Riuniti "
Bergamo, Italy
Cliniche Humanitas Gavazzeni
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

No publications provided

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT00985322     History of Changes
Other Study ID Numbers: ARCADIA, 2008-003529-17
Study First Received: September 25, 2009
Last Updated: March 6, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Mario Negri Institute for Pharmacological Research:
Hemodialysis

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

ClinicalTrials.gov processed this record on November 20, 2014