Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome

• Status: Completed
• Trial end date: 2011-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Erythropoietin (EPO) treatment in patients with the severe cardiorenal syndrome increases cardiac performance and decreases progression of renal failure by dampening the main driving forces of the cardiorenal syndrome in part via non-erythropoietic pathways.

I. Does EPO administration to patients with the severe cardiorenal syndrome increase cardiac performance and decrease progression of renal disease?

II. Does EPO treatment affect the main driving forces of the cardiorenal connection, that is, dampen the activated renin-angiotensin system (RAS), attenuate increased reactive oxygen species (ROS), normalize increased sympathetic activity, and decrease inflammation?

III. Does EPO treatment positively affect the cell function of patients with the cardiorenal syndrome:

1. are gene expression signatures of leukocytes positively influenced by EPO treatment,

2. does EPO shift the Jak/STAT pathway to a less pro-inflammatory profile in monocytes, and

3. are function and number of endothelial progenitor cells (EPCs) affected by treatment with EPO in the cardiorenal syndrome?

IV. Can the direct actions of EPO be differentiated from the effects on hemoglobin levels?

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UMC Utrecht
• Collaborator: Dutch Heart Foundation
• Treatments: Epoetin Alfa

Criteria

Inclusion Criteria:

• Patients with moderate renal failure (glomerular filtration rate [GFR] by Cockroft formula of 20-70 ml/min)

• Patients with heart failure NYHA class II-III-IV

• Hemoglobin (Hb) between 6.4 - 7.8 mmol/L in men and between 6.0 - 7.4 mmol/L in women

• Age > 18 years, < 80 years

• Written informed consent must be obtained from the subject or legally accepted representative before study-specific procedures, including screening procedures, are performed.

Exclusion Criteria:

• Therapy within 1 year before randomisation or any planned erythropoietic therapy between randomisation and study day 1

• Known intolerance to EPO administration

• Previously suspected of or confirmed to have neutralizing antibodies to recombinant human erythropoietin (rHuEPO)

• Uncontrolled hypertension (RR > 160 systolic, >100 diastolic)

• Forms of secondary hypertension other than renal hypertension

• Uncontrolled diabetes (HbA1c > 8.0 %)

• Primary dyslipidemia

• Kidney transplantation

• Proteinuria > 3.5 g/L

• Acute renal failure or rapidly progressive glomerulonephritis

• Hyperparathyroidism (parathyroid hormone [PTH] > 40)

• Bleeding or haemolysis as a cause of anaemia

• Deficiency of iron, folate, and/or vitamin B12

• Presence of chronic inflammatory disease or clinically significant infection

• Haematologic malignancy or solid tumour < 5 years ago

• Chronic liver disease

• Haemoglobinopathies

• Alcohol and/or drug abuse

• Enrolment in another study

• Child bearing potential (pre-menopausal woman who is not using adequate contraceptive precautions)

• Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures