Angiotensin-converting-enzyme (ACE) Inhibitors in Hemodialysis
ARCADIA
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)
2 other identifiers
interventional
269
1 country
29
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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2009
Longer than P75 for phase_3
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2009
CompletedFirst Submitted
Initial submission to the registry
September 25, 2009
CompletedFirst Posted
Study publicly available on registry
September 28, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedJanuary 11, 2021
January 1, 2021
6.9 years
September 25, 2009
January 8, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
Baseline, 1st and 2nd year
Secondary Outcomes (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
Baseline, 1st and 2nd year
Study Arms (2)
ACE inhibitor Ramipril
EXPERIMENTALnon-RAS inhibitor antihypertensive therapy
ACTIVE COMPARATORInterventions
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.
Blood Pressure lowering regimen not including RAS inhibitors
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (29)
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"
Milan, 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
Syracuse, Italy
P.O. G. Mazzini
Teramo, Italy
Related Publications (1)
Ruggenenti P, Podesta MA, Trillini M, Perna A, Peracchi T, Rubis N, Villa D, Martinetti D, Cortinovis M, Ondei P, Condemi CG, Guastoni CM, Meterangelis A, Granata A, Mambelli E, Pasquali S, Genovesi S, Pieruzzi F, Bertoli SV, Del Rosso G, Garozzo M, Rigotti A, Pozzi C, David S, Daidone G, Mingardi G, Mosconi G, Galfre A, Romei Longhena G, Pacitti A, Pani A, Hidalgo Godoy J, Anders HJ, Remuzzi G; ARCADIA Study Organization. Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial. Clin J Am Soc Nephrol. 2021 Apr 7;16(4):575-587. doi: 10.2215/CJN.12940820. Epub 2021 Mar 29.
PMID: 33782036DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Piero Ruggenenti, MD
Mario Negri Institute for Pharmacological Research
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 25, 2009
First Posted
September 28, 2009
Study Start
May 1, 2009
Primary Completion
April 1, 2016
Study Completion
April 1, 2016
Last Updated
January 11, 2021
Record last verified: 2021-01