Clinical trial NCT00827021: The Clinical Evaluation of the Dose of Erythropoietins Trial
Official title: Effects of the Dose of Erythropoiesis Stimulating Agents on Cardiac-cerebrovascular Outcomes Quality of Life and Costs in Hemodialysis Patients. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Failure, Chronic
Lead sponsor: Consorzio Mario Negri Sud
Sponsor class: OTHER
First posted: 2009-01-22
Enrollment: 656
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anaemia is a risk factor for death, cardiac-cerebrovascular events and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESAs) are the most used treatment option.

The purpose of this study is

1. the evaluation of biochemical markers to determine the efficacy of individual prediction of ESAs therapy
2. to determine the benefits and harms of different ESA doses therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD).

Detailed description: Phase III pragmatic, randomized-controlled trial comparing different doses of ESAs in patients with renal anaemia.

Study Sample:

Total of 900 participants from Italy

Background and Rationale:

Anaemia is a risk factor for death, cardiac-cerebrovascular events and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies higher haemoglobin (Hb) levels (around 10-13 g/dL) are associated with improved survival and quality of life compared to lower Hb levels (around 9 g/dL). Randomized studies have found that higher Hb targets, achieved and maintained with ESA, cause an increased risk of death, mainly due to adverse cardiac-cerebrovascular outcomes. It is possible that such effect is mediated by ESA dose. This hypothesis has not been formally tested and is the aim of the Clinical Evaluation of the DOSe of Erythropoietins (CEDOSE) trial.

CEDOSE is the first independent multicentre trial exploring the benefits and harms of different ESA doses therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD).

Hypothesis:

ESA resistance is associated with adverse vascular outcomes and poor quality of life in ESKD.

The CEDOSE trial will evaluate the biochemical markers to determine the efficacy of individual prediction of ESAs therapy; moreover it will evaluate the benefits and harms of two fixed ESA doses and explore the role of two treatment strategies, one based on a low and one based on a high ESA dose.

Interventions and Comparison:

Patients will be randomized 1:1 to 4000 IU/week iv. versus 18000 IU/week iv. of epoetin alfa, beta or any other epoetin in equivalent doses.

Eligibility criteria: Inclusion Criteria:

* Age \> = 18,
* End stage kidney disease and anemia
* Treatment with hemodialysis for renal replacement therapy
* no contraindications to erythropoietin stimulating agents (ESAs) or already treated with ESAs

Exclusion Criteria:

* Patients with Hb levels \> 10 g/dl without ESAs

Primary outcomes:
measure: TSAT (transferrin saturation), serum albumin, serum ferritin, serum transferrin, serum C reactive protein
timeFrame: after randomization at month 1, 2, 3, 6, 12
Secondary outcomes:
measure: Cardiovascular mortality
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: sudden death
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: Stroke
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: myocardial infarction
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: hospitalizations due to acute coronary syndrome, transitory ischemic attacks, not planned coronary revascularization, peripheric revascularization.
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: Thrombosis of the cardiovascular access
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: Seizures
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: Hypertensive events
timeFrame: after randomization at month 1, 2, 3, 6, 12
measure: Quality of life (QoL)
timeFrame: at randomization and at 6 and 12 months
measure: composite of all-cause mortality, non fatal myocardial infarction and stroke, hospitalizations due to acute coronary syndrome, transitory ischaemic attacks, not planned coronary revascularization procedures, peripheric revascularization procedures.
timeFrame: after randomization at month 1, 2, 3, 6, 12
Other outcomes:
Locations:
city: Acri
country: Italy
facility: Ospedale Beato Angelo
city: Agrigento
country: Italy
facility: Ospedale S. Giovanni Di Dio
city: Alghero
country: Italy
facility: Ospedale Civile di Alghero ASL n°1
city: Anzio
country: Italy
facility: Ospedali Riuniti di Anzio e Nettuno
city: Bellaria
country: Italy
facility: Ospedale Bellaria
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi
city: Brindisi
country: Italy
facility: "A. Perrino" Hospital
city: Chieri
country: Italy
facility: Ospedale Maggiore di Chieri ASL TO 5
city: Como
country: Italy
facility: Ospedale Sant'Anna, San Fermo Battaglia
city: Ferrara
country: Italy
facility: Ospedale Nuovo Sant'Anna
city: Foggia
country: Italy
facility: Azienda Ospedaliera Universitaria OO.RR Foggia
city: Formia
country: Italy
facility: P.O. SUD - Formia ASL Latina
city: Gorizia
country: Italy
facility: Ospedale S. Giovanni di Dio di Gorizia
city: Jesi
country: Italy
facility: Jesi (Carlo Urbani)
city: Ladispoli
country: Italy
facility: Centro Dialitico Diaverum, Ladispoli
city: Lanciano
country: Italy
facility: Ospedale Renzetti ASL Lanciano Vasto
city: Legnano
country: Italy
facility: Azienda ospedaliera Ospedale Civile di Legnano
city: Magenta
country: Italy
facility: Ospedale Fornaroli
city: Manduria
country: Italy
facility: Ospedale di Manduria
city: Marsala
country: Italy
facility: Centro Dialitico Diaverum Marsala
city: Martina Franca
country: Italy
facility: Ospedale Valle D'Itria ASL TA
city: Nicosia
country: Italy
facility: Ospedale di Nicosia
city: Novi Ligure
country: Italy
facility: Ospedale San Giacomo
city: Ortona
country: Italy
facility: Ospedale G. Bernabeo
city: Palermo
country: Italy
facility: Arnas Civico Di Cristina
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma
city: Parma
country: Italy
facility: Centro di Emodialisi ausl Parma
city: Pordenone
country: Italy
facility: Ospedale S. Maria degli Angeli
city: Priverno
country: Italy
facility: P.P.I. Priverno
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova, Reggio Emilia
city: Riesi
country: Italy
facility: Centro Dialitico Diaverum, Riesi
city: Rogliano
country: Italy
facility: Ospedale S. Barbara
city: Roma
country: Italy
facility: Ospedale S. Eugenio ASL RMC
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas, Rozzano
city: San Donato Milanese
country: Italy
facility: Policlinico San Donato
city: Sassari
country: Italy
facility: Ospedale SS Annunziata
city: Solofra
country: Italy
facility: Ospedale A.Landolfi
city: Terracina
country: Italy
facility: Ospedale Alfredo Fiorini di Terracina
city: Torino
country: Italy
facility: Azienda Ospedaliera C.T.O./C.R.F./ M. Adelaide
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
city: Vasto
country: Italy
facility: S. Pio da Pietrelcina
Study officials:
affiliation: Fondazione Mario Negri Sud
name: Giovanni FM Strippoli, MD
role: STUDY_CHAIR
References:
citation: Strippoli GF; Clinical Evaluation of the DOse of Erythropoietins Study Group (C.E. DOSE). Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol. Trials. 2010 Jun 9;11:70. doi: 10.1186/1745-6215-11-70.
citation: Saglimbene V, D'Alonzo D, Ruospo M, Vecchio M, Natale P, Gargano L, Nicolucci A, Pellegrini F, Craig JC, Triolo G, Procaccini DA, Santoro A, Di Giulio S, La Rosa S, Murgo A, Di Toro Mammarella R, Sambati M, D'Ambrosio N, Greco V, Giannoccaro G, Flammini A, Boccia E, Montalto G, Pagano S, Amaru S, Fici M, Lumaga GB, Mancini E, Veronesi M, Patregnani L, Querques M, Schiavone P, Chimienti S, Palumbo R, Di Franco D, Della Volpe M, Gori E, Salomone M, Iacono A, Moscoloni M, Treglia A, Casu D, Piras AM, Di Silva A, Mandreoli M, Lopez A, Quarello F, Catizone L, Russo G, Forcellini S, Maccarone M, Catucci G, Di Paolo B, Stingone A, D'Angelo B, Guastoni C, Pasquali S, Minoretti C, Bellasi A, Boscutti G, Martone M, David S, Schito F, Urban L, Di Iorio B, Caruso F, Mazzoni A, Musacchio R, Andreoli D, Cossu M, Li Cavoli G, Cornacchiari M, Granata A, Clementi A, Giordano R, Guastoni C, Barzaghi W, Valentini M, Hegbrant J, Tognoni G, Strippoli GF. [Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. the clinical evaluation of the DOSe of erythropoietins (C.E. DOSE) Trial]. G Ital Nefrol. 2013 Mar-Apr;30(2):gin/30.2.21. Italian.