Angiotensin-converting-enzyme (ACE) Inhibitors in Hemodialysis (ARCADIA)
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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) |
- 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 ]
- 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: | 266 |
| 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 |
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| Contact: Piero Ruggenenti, MD | piero.ruggenenti@marionegri.it |
| Italy | |
| Policlinico San Pietro | Recruiting |
| Ponte San Pietro, Bergamo, Italy | |
| Contact: Agnese Meterangelis, MD 0039035604400 dialisi.psp@virgilio.it | |
| Ospedale "Treviglio-Caravaggio" | Not yet recruiting |
| Treviglio, Bergamo, Italy | |
| Contact: Emilio Galli, MD 00390363424419 emilio_galli@ospedale.treviglio.bg.it | |
| Hospital of Montichiari | Recruiting |
| Montichiari, Brescia, Italy | |
| Principal Investigator: Francesco Scolari, MD | |
| Presidio Ospedaliero Acireale | Recruiting |
| Acireale, Catania, Italy | |
| Contact: Maurizio Garozzo, MD 00390957677115 mauriziocom@hotmail.com | |
| Hospital "Morgagni-Pierantoni" | Recruiting |
| Forlì, Forlì Cesena, Italy | |
| Contact: Giovanni Mosconi, MD 0039 0543 735313 giovanni.mosconi@ausl.fo.it | |
| Sub-Investigator: Loretta Zambianchi, MD | |
| Principal Investigator: Giovanni Mosconi, MD | |
| A.O. Desio e Vimercate | Recruiting |
| Desio, MB, Italy | |
| Principal Investigator: Renzo Scanziani, MD | |
| Ospedale "Caduti Bollatesi" | Recruiting |
| Bollate, Milano, Italy | |
| Contact: Ugo Teatini, MD 003902994305200 uteatini@aogarbagnate.lombardia.it | |
| Hospital of Cernusco sul Naviglio | Recruiting |
| Cernusco sul Naviglio, Milano, Italy | |
| Principal Investigator: Ferruccio Conte, MD | |
| Hospital "Bassini" | Recruiting |
| Cinisello Balsamo, Milano, Italy | |
| Principal Investigator: Claudio Pozzi, MD | |
| A.O. Ospedale Civile di Legnano | Recruiting |
| Legnano, Milano, Italy | |
| Contact: Carlo Maria Guastoni, MD 00390331449111 carlo.guastoni@ao-legnano.it | |
| A.O. della Provincia di Lodi | Not yet recruiting |
| Lodi, Milano, Italy | |
| Contact: Marco Farina, MD 00390371372252 marco.farina@ao.lodi.it | |
| Presidio Ospedaliero di Magenta | Recruiting |
| Magenta, Milano, Italy | |
| Contact: Carlo Maria Guastoni, MD 003902979631 carlo.guastoni@ao-legnano.it | |
| IRCCS "Humanitas" | Recruiting |
| Rozzano, Milano, Italy | |
| Contact: Salvatore Badalamenti, MD 00390282241 salvatore.badalamenti@humanitas.it | |
| Principal Investigator: Salvatore Badalamenti, MD | |
| IRCCS Multimedia | Recruiting |
| Sesto San Giovanni, Milano, Italy | |
| Principal Investigator: Silvio Bertoli, MD | |
| Fondazione San Raffaele Monte Tabor | Recruiting |
| Milan, MI, Italy | |
| Contact: Donatella Spotti, MD 0039 0226433006 donatella.spotti@hsr.it | |
| Principal Investigator: Donatella Spotti, MD | |
| Ospedale San Giovanni di Dio | Recruiting |
| Agrigento, Italy | |
| Contact: Antonio Granata, MD 0039 0922442292 antonio.granata4@tin.it | |
| Principal Investigator: Antonio Granata, MD | |
| Cliniche Humanitas Gavazzeni | Recruiting |
| Bergamo, Italy | |
| Contact: Giulio Mingardi, MD 0039 035 322376 giulio.mingardi@gavazzeni.it | |
| Principal Investigator: Giulio Mingardi, 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" | Withdrawn |
| Brescia, Italy | |
| ASL 8 - S.C. Territoriale di Nefrologia e Dialisi | Recruiting |
| Cagliari, Italy | |
| Contact: Piergiorgio Bolasco, MD 0039 0706097341 pg.bolasco@tin.it | |
| Principal Investigator: Piergiorgio Bolasco, MD | |
| A.O. Giuseppe Brotzu | Recruiting |
| Cagliari, Italy | |
| Contact: Antonello Pani, MD 0039 070539491 antonellopani@aob.it | |
| Principal Investigator: Antonello Pani, MD | |
| Hospital "Sant'Anna" | Withdrawn |
| Como, Italy | |
| A.O. S. Croce e Carle, Cuneo | Recruiting |
| Cuneo, Italy | |
| Contact: Alfonso Pacitti, MD 00390171616240 pacitti.a@ospedale.cuneo.it | |
| Hospital "San Paolo" | Recruiting |
| Milano, Italy | |
| Principal Investigator: Daniele Cusi, MD | |
| 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 "Azienda Ospedaliera Universitaria Di Parma" | Recruiting |
| Parma, Italy | |
| Principal Investigator: Salvatore David, MD | |
| ASL of Ravenna | Withdrawn |
| Ravenna, Italy | |
| Arcispedale Santa Maria Nuova | Recruiting |
| Reggio Emilia, Italy | |
| Contact: Sonia Pasquali, MD 0039 0522 296379 pasquali.sonia@asmn.re.it | |
| Principal Investigator: Sonia Pasquali, MD | |
| Hospital "Degli Infermi" | Recruiting |
| Rimini, Italy | |
| Principal Investigator: Angelo Rigotti, MD | |
| A.O. Umberto I | Recruiting |
| Siracusa, Italy | |
| Principal Investigator: Giuseppe Daidone, MD | |
| Hospital "Az. Osp. Valtellina e Valchiavenna" | Withdrawn |
| Sondrio, Italy | |
| P.O. G. Mazzini | Recruiting |
| Teramo, Italy | |
| Contact: Goffredo Del Rosso, MD 0039 0861429748 goffredo.delrosso@aslteramo.it | |
| Principal Investigator: Goffredo Del Rosso, MD | |
| 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: | February 21, 2013 |
| 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 Vascular Diseases Cardiovascular Diseases Pathological Conditions, Anatomical Cardiomegaly Heart Diseases Angiotensin-Converting Enzyme Inhibitors |
Ramipril Antihypertensive Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Cardiovascular Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on June 18, 2013