The Clinical Evaluation of the Dose of Erythropoietins Trial (CEDOSE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Giovanni FM Strippoli, MD, Consorzio Mario Negri Sud
ClinicalTrials.gov Identifier:
NCT00827021
First received: January 21, 2009
Last updated: July 15, 2016
Last verified: July 2016
  Purpose

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).

Condition Intervention Phase
Kidney Failure, Chronic
Drug: Erythropoiesis Stimulating Agents (ESAs): epoetin alfa, beta or any other epoetin in equivalent dose.
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Consorzio Mario Negri Sud:

Primary Outcome Measures:
  • TSAT (transferrin saturation), serum albumin, serum ferritin, serum transferrin, serum C reactive protein [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cardiovascular mortality [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]
  • sudden death [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]
  • Stroke [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]
  • myocardial infarction [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]
  • hospitalizations due to acute coronary syndrome, transitory ischemic attacks, not planned coronary revascularization, peripheric revascularization. [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]
  • Thrombosis of the cardiovascular access [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: Yes ]
  • Seizures [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: Yes ]
  • Hypertensive events [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: Yes ]
  • Quality of life (QoL) [ Time Frame: at randomization and at 6 and 12 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: after randomization at month 1, 2, 3, 6, 12 ] [ Designated as safety issue: No ]

Enrollment: 656
Study Start Date: July 2009
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ESAs 1 low dose 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
Active Comparator: ESAs 2 high dose 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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827021

Locations
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, Italy
Sponsors and Collaborators
Giovanni FM Strippoli, MD
Investigators
Study Chair: Giovanni FM Strippoli, MD Fondazione Mario Negri Sud
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Giovanni FM Strippoli, MD, MD, Consorzio Mario Negri Sud
ClinicalTrials.gov Identifier: NCT00827021     History of Changes
Other Study ID Numbers: FARM6X822T  2008-006014-20 
Study First Received: January 21, 2009
Last Updated: July 15, 2016
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Epoetin Alfa
Hematinics

ClinicalTrials.gov processed this record on August 22, 2016