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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Consorzio Mario Negri Sud
Sponsor:
Information provided by (Responsible Party):
Consorzio Mario Negri Sud
ClinicalTrials.gov Identifier:
NCT00827021
First received: January 21, 2009
Last updated: December 4, 2012
Last verified: December 2012
  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 ]

Estimated Enrollment: 900
Study Start Date: June 2009
Estimated Primary Completion Date: December 2013 (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
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

Contacts
Contact: Giovanni FM Strippoli, MD +39 0872 570 ext 356 strippoli@negrisud.it

Locations
Italy
"A. Perrino" Hospital Recruiting
Brindisi, Italy, 72100
Contact: Palmira Schiavone, MD    +39 0831 537355    palmiraschiavone@libero.it   
Principal Investigator: Palmira Schiavone, MD         
Azienda Ospedaliera Universitaria OO.RR Foggia Not yet recruiting
Foggia, Italy, 71100
Contact: Giuseppe Grandaliano, MD    0881 736034    grandaliano@unifg.it   
Principal Investigator: Giuseppe Grandaliano, MD         
Sponsors and Collaborators
Consorzio Mario Negri Sud
Investigators
Study Chair: Giovanni FM Strippoli, MD Consorzio Mario Negri Sud
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: 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: December 4, 2012
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014