E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Chronic Kidney Disease (CKD) not yet on dialysis |
pazienti con Malattia Renale Cronica (MRC) non ancora in dialisi |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Chronic Kidney Disease (CKD) not yet on dialysis |
pazienti con Malattia Renale Cronica (MRC) non ancora in dialisi |
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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 | LLT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 100000004857 |
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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 |
determine whether, in patients with Chronic Kidney Disease (CKD) not yet on dialysis, achieve and maintain in a relatively early stage of chronic kidney levels of phosphorus to the lower limit of normal and still below what is recommended by current guidelines, involves a reduction in the rate of progression of CKD and therefore the number of people who come to dialysis and CV mortality, which weighs heavily on patients with CKD.
The primary objective of the study is to compare the control group and the intervention group compared to 'end point composite of death from any cause and from the entrance on dialysis. |
verificare se, nei pazienti con Malattia Renale Cronica (MRC) non ancora in dialisi, raggiungere e mantenere in una fase relativamente precoce della MRC dei livelli di fosforemia ai limiti inferiori della norma e comunque al di sotto di quanto raccomandato dalle attuali Linee Guida, comporta una riduzione della velocità di progressione della MRC e quindi del numero di soggetti che arrivano alla dialisi e della mortalità CV, che grava pesantemente sui pazienti con MRC.
L’obiettivo primario dello studio è confrontare il gruppo di controllo e il gruppo di intervento rispetto all’ end point composito, costituito dal decesso per qualunque causa e dall’ingresso in dialisi. |
|
E.2.2 | Secondary objectives of the trial |
- changes in serum phosphorus, changes in fractional urine phosphorus excretion, in serum parathyroid hormone, and FGF-23
- annual decline in GFR
- cardiovascular events: (acute myocardial infarction, stroke, coronary arterial revascularization)
- changes in arterial calcifications by using Kauppila score |
1. variazioni dei parametri del metabolismo minerale: fosforemia, escrezione frazionale del fosfato, paratormone, FGF-23
2. perdita annua di VFG
3. comparsa di eventi cardiovascolari fatali e non, comprendendo in questi l’IMA, ictus cerebri, procedure di rivascolarizzazione coronarica- vedi Appendice 3)
4. valutare se il trattamento dell’iperfosforemia riduce o arresta il deterioramento del sistema cardiovascolare (progressione delle calcificazioni vascolari mediante lo score di Kauppila |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with CKD not requiring dialysis and with eGFR of 15-60 ml/.min/1.73m2 by using CKD-EPI equation and phosphorus level >3,8 mg/dL
- Patients have to be aged 18 years or older
- Patients should be willing and able to provide written informed consent to participate in study |
- pazienti adulti affetti da MRC con VFG stimatocon formula CKD-EPI [21] tra 60 e 15 mL/min, ed una fosforemia >di 3,8 mg/dL, non ancora in trattamento dialitico
- Età > 18 anni
- Consenso informato scritto
- Raggiungimento dei target, terapeutici in accordo con la GCP nefrologica e cioè PAS compresa tra 130 e 140 mmHg e PAD compresa tra 80 e <90 mmHg, Hb > 11 g/dL, bicarbonatemia tra 20 e 24 mEq/L, colesterolo totale < 200 mg/dL |
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E.4 | Principal exclusion criteria |
- Patients with current malignancy
- Women who are pregnant, capable of becoming pregnant and not participating in an acceptable form of birth control
- Patients with chronic gastrointestinal diseases that could impede their absorptive ability such as Crohn's disease, ulcerative colitis and sprue
- Patients who have liver insufficiency
- Patients with a history of solid organ transplantation
- Patients with a rapid changes of GFR (more than - 5 mL/min within 90 days of enrollment in this study )
- Patients with PTH > 500 pcg/mL
- Patients with a persistent hypercalcemia (> 11 mg/dL)
- Patients in maintenance therapy with phosphate binders
- Subjects with a non-compliance to dietary and pharmacological prescriptons
- Subjects who are unable to independently provide written informed consent
- Subjects with inability to perform a urinary collection of 24 hours
- Patients with malnutrition (plasma albumin < 3 g/dL)
- Patients with proteinuria > 2g/24 hours
- Patients currently participating in a clinical trial with another investigational drug or device or who have receiving an investigational drug or device within 90 days of enrollment in this study |
soggetti con neoplasie “attive” ;
# donne in stato di gravidanza;
# malattie infiammatorie croniche intestinali;
# insufficienza epatica;
# anamnesi di portatore di trapianto di organi solidi e/o utilizzo di farmaci immunosoppressori;
# soggetti con MRC cosiddetti fast progressors, cioè con perdita di VFG stimato (formula CKD-EPI) > di 5 mL/min nei 3 mesi precedenti l’arruolamento;
# PTH > 500 pg/mL;
# ipercalcemia persistente > 11 mg/dL
# soggetti già in trattamento con farmaci chelanti del fosforo
# soggetti scarsamente aderenti alle prescrizioni farmacologiche e dietetiche;
# pazienti con gravi condizioni cliniche che controindichino la partecipazione del paziente allo studio, secondo giudizio dello sperimentatore;
# impossibilità/incapacità di raccogliere le urine di 24 ore
# malnutrizione con livelli di albuminemia < 3 g/dL
# proteinuria > 2 g/die
# utilizzo di farmaci sperimentali negli ultimi 3 mesi prima dell’inclusione nello studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
percentage of composite events (death from any cause and any input on dialysis) and composite event time, starting from the entrance into the study. All efficacy assessments will be carried out in accordance with the principle of 'Intention-to-treat analysis (evaluation of all patients initially randomized to one of two types of treatment (usual care or intensive treatment of phosphorus) irrespective of the completion of the study and regardless of the assumption of a rescue therapy. addition Intention-to-treat analysis, an analysis will be performed per protocol patients who completed the study. This endpoint is considered to be of utmost clinical importance because it represents the combination of the two possible events that can occur in CKD 3-5. This outcome will be assessed by the investigator and documented in the CRF |
percentuale di eventi compositi (morte per qualsiasi causa e ingresso in dialisi) e tempo all’evento composito, a partire dall’ingresso nello studio. Tutte le valutazioni di efficacia saranno eseguite in base al principio dell' Intention-to-treat (valutazione di tutti i pazienti inizialmente randomizzati ad uno dei due tipi di trattamento (usual care o trattamento intensivo della fosforemia) a prescindere dal completamento dello studio ed a prescindere dall’assunzione di una rescue therapy. Oltre all’analisi Intention to treat, verrà effettuata una analisi per protocol nei pazienti che hanno completato lo studio. Questo endpoint è considerato di estrema rilevanza clinica in quanto rappresenta la combinazione dei due possibili eventi che possono verificarsi in CKD 3-5. Questo esito verrà valutato dagli sperimentatori e documentato nella CRF |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. variations in the parameters of mineral metabolism: phosphorus, fractional excretion of phosphate, PTH, FGF-23
2. annual loss of GFR
3. occurrence of fatal cardiovascular events or otherwise, including those in the AMI, stroke cerebri, coronary revascularization procedures-see Appendix 3)
4. evaluate whether the treatment of hyperphosphatemia reduces or stops the deterioration of the cardiovascular system (progression of vascular calcification by the score of Kauppila |
1. variazioni dei parametri del metabolismo minerale: fosforemia, escrezione frazionale del fosfato, paratormone, FGF-23
2. perdita annua di VFG
3. comparsa di eventi cardiovascolari fatali e non, comprendendo in questi l’IMA, ictus cerebri, procedure di rivascolarizzazione coronarica- vedi Appendice 3)
4. valutare se il trattamento dell’iperfosforemia riduce o arresta il deterioramento del sistema cardiovascolare (progressione delle calcificazioni vascolari mediante lo score di Kauppila |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
dieta a contenuto ridotto di fosfati |
diet reduced content of phosphates |
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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 | 12 |
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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LVLS=Last patient last treatment |
LVLS=Last patient last treatment |
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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 | 32 |
E.8.9.1 | In the Member State concerned days | 0 |