The Clinical Evaluation of the Dose of Erythropoietins Trial

NCT ID: NCT00827021

Last Updated: 2016-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 656 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2014-07-31

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.

Conditions

Kidney Failure, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ESAs 1 low dose

Group Type: EXPERIMENTAL

Erythropoiesis Stimulating Agents (ESAs): epoetin alfa, beta or any other epoetin in equivalent dose.

Intervention Type: DRUG

4000 IU/week I.V. Until the end of the trial

ESAs 2 high dose

Group Type: ACTIVE_COMPARATOR

Erythropoiesis Stimulating Agents (ESAs): epoetin alfa, beta or any other epoetin in equivalent dose.

Intervention Type: DRUG

18000 IU/week I.V. Until the end of the trial

Interventions

Erythropoiesis Stimulating Agents (ESAs): epoetin alfa, beta or any other epoetin in equivalent dose.

4000 IU/week I.V. Until the end of the trial

Intervention Type: DRUG

Erythropoiesis Stimulating Agents (ESAs): epoetin alfa, beta or any other epoetin in equivalent dose.

18000 IU/week I.V. Until the end of the trial

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Giovanni FM Strippoli, MD

OTHER

Sponsor Role: lead

Responsible Party

Giovanni FM Strippoli, MD

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Giovanni FM Strippoli, MD

Role: STUDY_CHAIR

Fondazione Mario Negri Sud

Locations

Ospedale Beato Angelo

Acri, , Italy

Ospedale S. Giovanni Di Dio

Agrigento, , Italy

Ospedale Civile di Alghero ASL n°1

Alghero, , Italy

Ospedali Riuniti di Anzio e Nettuno

Anzio, , Italy

Ospedale Bellaria

Bellaria, , Italy

Policlinico S. Orsola - Malpighi

Bologna, , Italy

"A. Perrino" Hospital

Brindisi, , Italy

Ospedale Maggiore di Chieri ASL TO 5

Chieri, , Italy

Ospedale Sant'Anna, San Fermo Battaglia

Como, , Italy

Ospedale Nuovo Sant'Anna

Ferrara, , Italy

Azienda Ospedaliera Universitaria OO.RR Foggia

Foggia, , Italy

P.O. SUD - Formia ASL Latina

Formia, , Italy

Ospedale S. Giovanni di Dio di Gorizia

Gorizia, , Italy

Jesi (Carlo Urbani)

Iesi, , Italy

Centro Dialitico Diaverum, Ladispoli

Ladispoli, , Italy

Ospedale Renzetti ASL Lanciano Vasto

Lanciano, , Italy

Azienda ospedaliera Ospedale Civile di Legnano

Legnano, , Italy

Ospedale Fornaroli

Magenta, , Italy

Ospedale di Manduria

Manduria, , Italy

Centro Dialitico Diaverum Marsala

Marsala, , Italy

Ospedale Valle D'Itria ASL TA

Martina Franca, , Italy

Ospedale di Nicosia

Nicosia, , Italy

Ospedale San Giacomo

Novi Ligure, , Italy

Ospedale G. Bernabeo

Ortona, , Italy

Arnas Civico Di Cristina

Palermo, , Italy

Azienda Ospedaliera Universitaria di Parma

Parma, , Italy

Centro di Emodialisi ausl Parma

Parma, , Italy

Ospedale S. Maria degli Angeli

Pordenone, , Italy

P.P.I. Priverno

Priverno, , Italy

Arcispedale S. Maria Nuova, Reggio Emilia

Reggio Emilia, , Italy

Centro Dialitico Diaverum, Riesi

Riesi, , Italy

Ospedale S. Barbara

Rogliano, , Italy

Ospedale S. Eugenio ASL RMC

Roma, , Italy

Istituto Clinico Humanitas, Rozzano

Rozzano, , Italy

Policlinico San Donato

San Donato Milanese, , Italy

Ospedale SS Annunziata

Sassari, , Italy

Ospedale A.Landolfi

Solofra, , Italy

Ospedale Alfredo Fiorini di Terracina

Terracina, , Italy

Azienda Ospedaliera C.T.O./C.R.F./ M. Adelaide

Torino, , Italy

Ospedale San Giovanni Bosco

Torino, , Italy

S. Pio da Pietrelcina

Vasto, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 20534124 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23832463 (View on PubMed)

Other Identifiers

2008-006014-20

Identifier Type: -

Identifier Source: secondary_id

FARM6X822T

Identifier Type: -

Identifier Source: org_study_id