The Clinical Evaluation of the Dose of Erythropoietins Trial

Kidney Failure, Chronic Clinical Trial

— CEDOSE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00827021
• Other study ID #: FARM6X822T
• Secondary ID: 2008-006014-20
• Status: Completed
• Phase: Phase 3
• First received: January 21, 2009
• Last updated: July 15, 2016
• Start date: July 2009
• Est. completion date: July 2014

Study information

• Verified date: July 2016
• Source: Consorzio Mario Negri Sud
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 656
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Italy	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)	Jesi
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

Sponsors (1)

Lead Sponsor	Collaborator
Giovanni FM Strippoli, MD

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TSAT (transferrin saturation), serum albumin, serum ferritin, serum transferrin, serum C reactive protein		after randomization at month 1, 2, 3, 6, 12	No
Secondary	Cardiovascular mortality		after randomization at month 1, 2, 3, 6, 12	No
Secondary	sudden death		after randomization at month 1, 2, 3, 6, 12	No
Secondary	Stroke		after randomization at month 1, 2, 3, 6, 12	No
Secondary	myocardial infarction		after randomization at month 1, 2, 3, 6, 12	No
Secondary	hospitalizations due to acute coronary syndrome, transitory ischemic attacks, not planned coronary revascularization, peripheric revascularization.		after randomization at month 1, 2, 3, 6, 12	No
Secondary	Thrombosis of the cardiovascular access		after randomization at month 1, 2, 3, 6, 12	Yes
Secondary	Seizures		after randomization at month 1, 2, 3, 6, 12	Yes
Secondary	Hypertensive events		after randomization at month 1, 2, 3, 6, 12	Yes
Secondary	Quality of life (QoL)		at randomization and at 6 and 12 months	No
Secondary	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.		after randomization at month 1, 2, 3, 6, 12	No