E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
End stage renal disease |
Insufficienza renale terminale |
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E.1.1.1 | Medical condition in easily understood language |
End stage renal disease |
Insufficienza renale terminale |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029151 |
E.1.2 | Term | Nephropathy |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess whether, at comparable BP control, ACE inhibitor as compared to non-RAS inhibitor therapy reduces the incidence of a combined end-point of CV death (including sudden cardiac death and cardiac arrest resuscitation) and myocardial infarction or non-fatal stroke. |
- Valutare se, a livelli paragonabili di controllo pressorio, la terapia con ACE inibitori riduce in modo piu` significativo rispetto alla terapia con farmaci che non agiscono sul Sistema Renina-Angiotensina l`incidenza di end point compositi di morte per eventi cardiovascolari (inclusa la morte improvvisa e ripresa dopo arresto cardiaco) e infarto del miocardio o ictus non fatale. |
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E.2.2 | Secondary objectives of the trial |
- To compare the incidence of the single components of the combined end-point, of myocardial or peripheral revascularizations, new onset of atrial fibrillation in one of its three forms (paroxysmal, persistent and permanent) or recurrence of the arrhythmia in patients who experienced paroxysmal or persistent atrial fibrillation previously, hospitalizations for chronic heart failure and thrombosis of the artero-venous fistula. - To evaluate whether ACE inhibitors limit progression or achieve regression of LVH and ameliorate some of the components of the metabolic syndrome and whether these effects correlates with CV outcomes. - To compare the cost/effectiveness of the two treatments. |
Obiettivi secondari- Paragonare l`incidenza delle singole componenti degli end point combinati,della rivascolarizzazione del miocardio o periferica,fibrillazione atriale parossistica di nuova insorgenza o persistente,ospedalizzazioni per malattia cardiaca cronica e trombosi della fistola artero-venosa.- Valutare se la terapia con ACE inibitori limita la progressione o permette la regressione di LVH e migliora alcuni dei componenti della sindrome metabolica e se questi effetti correlano con gli outcome cardiovascolari.- Paragonare il rapporto costo/efficacia dei due trattamenti. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
- Uomini e donne di eta` superiore ai 18 anni, che siano sottoposti a emodialisi ( due o tre sedute alla settimana) da almeno sei mesi - Ipertensione (pressione sistolica/diastolica >140/90 mmHg o pressione sistolica/diastolica post-dialisi >130/80 mmHg o terapia antiipertensiva in corso) e/o - Ipertrofia ventricolare sinistra definita come indice di massa cardiaca >130 g/m2 per gli uomini e > 100 g/m2 per le donne nei tre mesi precedenti l`arruolamento nello studio - Consenso informato scritto |
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E.4 | Principal 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 |
- Specifiche indicazioni (come l`insufficienza cardiaca) o controindicazioni (come l`ipersensibilita`) alla terapia con ACE inibitori - Terapia concomitante con ACE inibitori e antagonisti recettorilai dell`angiotensina II - Iperpotassemia (potassio sierico >6mEq/L) nonostante un controllo ottimale dell`acidosi metabolica e della glicemia (nei diabetici) in pazienti che fanno meno di tre sedute dialitiche alla settimana. - Ipotensione sintomatica cronica o intradialitica - Aritmia che a giudizio del medico potrebbe essere peggiorata dall`iperpotassemia (come bradicardia sinusale, conduzione atrio-ventriculare ritardata, blocco atrio-ventriculare) - Eventi cardiovascolari (ictus, infarto acuto del miocardio o altre sindromi coronariche) negli ultimi tre mesi - Iper- o ipo-tiroidismo non controllati - Patologia sistemica attiva, tumori e qualunque altra condizione clinica che si associ ad un`aspettativa di vita inferiore ai due anni - Uso di droghe o abuso di alcool , malattie psichiatriche e incapacita` a comprendere i potenziali rischi e i benefici derivati dalla partecipazione allo studio; - Gravidanza, allattamento o donne potenzialmente fertili che non facciano uso di un sistema di contraccezione ritenuto scientificamente valido. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
L'end point principale sara' un end point combinato di morte cardiovascolare (comprendente la morte improvvisa e la ripresa dopo arresto cardiaco)e l'infarto o l'ictus non fatale. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At randomization and then every three months. |
Alla randomizzazione e poi ogni 3 mesi. |
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E.5.2 | Secondary end point(s) |
- Incidence of the single components of the combined end-point, of myocardial or peripheral revascularizations, new onset of atrial fibrillation2 in one of its three forms (paroxysmal, persistent and permanent) or recurrence of the arrhythmia in patients who experienced paroxysmal or persistent atrial fibrillation previously, hospitalizations for chronic heart failure3 and thrombosis of the artero-venous fistula. |
Incidenza delle singole componenti degli end point combinati, della rivascolarizzazione del miocardio o periferica, fibrillazione atriale parossistica di nuova insorgenza o persistente, ospedalizzazioni per malattia cardiaca cronica e trombosi della fistola artero-venosa. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At randomization, 12 and 24 months. |
Alla randomizzazione, a 12 mesi e a 24 mesi. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
disegno PROBE |
PROBE design |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 37 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 42 |
E.8.9.1 | In the Member State concerned days | 0 |