Angiotensin-converting-enzyme (ACE) Inhibitors in Hemodialysis - Full Text View

Sponsor:	Mario Negri Institute for Pharmacological Research
Collaborator:	Agenzia Italiana del Farmaco
Information provided by:	Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:	NCT00985322

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: The study 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 hypertensive chronic dialysis patients with left ventricular hypertrophy (LVH). 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, 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: This prospective, randomized, open label, blinded end point (PROBE) trial will include 624 hypertensive ESRD patients with echocardiography evidence of LVH who are on chronic hemodialysis since >6 months. After 1 month wash-out period from previous RAS inhibitor therapy and stratification for diabetes YES/NO, they will have a baseline evaluation of main clinical and laboratory parameters and will be randomized to 2-year treatment with an ACE inhibitor or a BP lowering regimen not including RAS inhibitors.

Expected results: ACE inhibitor compared to non-RAS inhibitor therapy is expected to reduce more effectively fatal and non-fatal CV events, limit progression or induce regression of LVH, improve some components of the metabolic syndrome, and reduce treatment costs for cardiovascular complications.

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

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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 (ARCADIA Study)

Resource links provided by NLM:

MedlinePlus related topics: Atrial Fibrillation Blood Pressure Medicines Dialysis Fistulas Heart Attack High Blood Pressure Kidney Failure

Drug Information available for: Ramipril

U.S. FDA Resources

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 ]

Estimated Enrollment:	628
Study Start Date:	May 2009
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
ACE inhibitor Ramipril: Experimental	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.
non-RAS inhibitor antihypertensive therapy: Active Comparator	Drug: non-RAS inhibitor antihypertensive therapy Blood Pressure lowering regimen not including RAS inhibitors

Show Detailed Description

Eligibility

Ages Eligible for Study:	50 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Men and post-menopausal women 50 to 80 years of age who are on chronic hemodialysis since at least 6 months with three 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)
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).
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00985322

Contacts

Contact: Piero Ruggenenti, MD

piero.ruggenenti@marionegri.it

Locations

Italy
Hospital "San Gerardo"	Recruiting
Monza, Italy
Contact: Simonetta Genovesi, MD simonetta.genovesi@unimib.it
Principal Investigator: Andrea Stella, MD
Sub-Investigator: Simonetta Genovesi, MD
Sub-Investigator: Erica Casiraghi, MD
Hospital "Ospedali Riuniti "	Recruiting
Bergamo, Italy
Contact: Piero Ruggenenti, MD pruggenenti@ospedaliriuniti.bergamo.it
Sub-Investigator: Patrizia Ondei, MD
Sub-Investigator: Donatella Marchesi, MD
Sub-Investigator: Stefano Rota, MD
Hospital "Policlinico S.Orsola-Malpighi"	Recruiting
Bologna, Italy
Contact: Antonio Santoro, MD antonio.santoro@aosp.bo.it
Principal Investigator: Antonio Santoro, MD
Sub-Investigator: Elena Mancini, MD
Hospital "Spedali Civili"	Not yet recruiting
Brescia, Italy
Principal Investigator: Giovanni Cancarini, MD
ASL of Ravenna	Not yet recruiting
Ravenna, Italy
Principal Investigator: Giuseppe Emiliani, MD
Hospital "San Carlo Borromeo"	Not yet recruiting
Milano, Italy
Principal Investigator: Daniele Cusi, MD
IRCCS "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena	Not yet recruiting
Milano, Italy
Principal Investigator: Piergiorgio Messa, MD
Hospital "Azienda Ospedaliera Universitaria Di Parma"	Not yet recruiting
Parma, Italy
Principal Investigator: Salvatore David, MD
Hospital "San Paolo"	Not yet recruiting
Milano, Italy
Principal Investigator: Diego Brancaccio, MD
Hospital "Degli Infermi"	Not yet recruiting
Rimini, Italy
Principal Investigator: Leonardo Cagnoli, MD
Hospital "Az. Osp. Valtellina e Valchiavenna"	Not yet recruiting
Sondrio, Italy
Principal Investigator: Vincenzo De Cristofaro, MD
Italy, Bergamo
Hospital "Bolognini"	Not yet recruiting
Seriate, Bergamo, Italy
Principal Investigator: Luciano Pedrini, MD
Italy, Bologna
ASL of Imola	Not yet recruiting
Imola, Bologna, Italy
Principal Investigator: Alessandro Zuccalà, MD
Italy, Brescia
Hospital of Montichiari	Not yet recruiting
Montichiari, Brescia, Italy
Principal Investigator: Francesco Scolari, MD
Italy, Forlì Cesena
Hospital "Morgagni-Pierantoni"	Recruiting
Forlì, Forlì Cesena, Italy
Contact: Sauro Urbini, MD surbini@ausl.fo.it
Principal Investigator: Sauro Urbini, MD
Sub-Investigator: Loretta Zambianchi, MD
Italy, Milano
Hospital "Bassini"	Not yet recruiting
Cinisello Balsamo, Milano, Italy
Principal Investigator: Claudio Pozzi, MD
IRCCS Multimedia	Not yet recruiting
Sesto San Giovanni, Milano, Italy
Principal Investigator: Silvio Bertoli, MD
Hospital of Cernusco sul Naviglio	Not yet recruiting
Cernusco sul Naviglio, Milano, Italy
Principal Investigator: Ferruccio Conte, MD
IRCCS "Humanitas"	Not yet recruiting
Rozzano, Milano, Italy
Principal Investigator: Giorgio Graziani, MD

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:	Clinical Research Center for Rare Diseases "Aldo and Cele daccò" ( Mario Negri Institute for Pharmacological Research )
Study ID Numbers:	ARCADIA
Study First Received:	September 25, 2009
Last Updated:	September 25, 2009
ClinicalTrials.gov Identifier:	NCT00985322 History of Changes
Health Authority:	Italy: Ministry of Health

Keywords provided by Mario Negri Institute for Pharmacological Research:

Hemodialysis

Additional relevant MeSH terms:

Pathological Conditions, Anatomical
Hypertrophy, Left Ventricular
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Vascular Diseases
Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions

Ramipril
Protease Inhibitors
Hypertrophy
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Cardiovascular Diseases
Cardiomegaly
Hypertension

ClinicalTrials.gov processed this record on February 08, 2010