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

Giovanni FM Strippoli, MD

Status and phase: Completed; Phase 3

Conditions: Kidney Failure, Chronic

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

Study type: Interventional

Funder types: Other

Identifiers

NCT00827021

2008-006014-20

FARM6X822T

Details and patient eligibility

About

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).

Full 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.

Enrollment: 656 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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656 participants in 2 patient groups

ESAs 1 low dose

Experimental group

Treatment:

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

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

ESAs 2 high dose

Active Comparator group

Treatment:

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

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