NCT00356733

Brief 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. 1.are gene expression signatures of leukocytes positively influenced by EPO treatment,
  2. 2.does EPO shift the Jak/STAT pathway to a less pro-inflammatory profile in monocytes, and
  3. 3.are function and number of endothelial progenitor cells (EPCs) affected by treatment with EPO in the cardiorenal syndrome?

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2007

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 25, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 26, 2006

Completed
5 months until next milestone

Study Start

First participant enrolled

January 1, 2007

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2011

Completed
Last Updated

December 2, 2011

Status Verified

November 1, 2011

Enrollment Period

4.5 years

First QC Date

July 25, 2006

Last Update Submit

November 30, 2011

Conditions

Heart Failure, CongestiveRenal Insufficiency, Chronic

Keywords

cardiorenal syndromeerythropoietinHeart Failure, CongestiveRenal Insufficiency, Chronic

Outcome Measures

Primary Outcomes (1)

  • changes in gene-arrays, EPC and biomarkers panels

    14 days, 6 and 12 months

Secondary Outcomes (2)

  • cardiac performance and renal function

    6 and 12 months

  • QoL

    6 and 12 months

Study Arms (3)

EPO rise

EXPERIMENTAL

EPO administration

Drug: Erythropoietin administration

EPO stable

EXPERIMENTAL

EPO and stable Hemoglobin

Drug: Erythropoietin administration

control

NO INTERVENTION

standard treatment

Interventions

Erythropoietin administrationDRUG

50 IU/kg/week EPO to a target haemoglobin level of 13.7 g/dL for men and 13.4 g/dL for women (group A) or to a target comparable to starting hemoglobin level (group B)

EPO riseEPO stable

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Meander Medical Center Amersfoort

Amersfoort, Utrecht, 3800 BM, Netherlands

Location

Univ. Medical Center Utrecht

Utrecht, Utrecht, 3508 GA, Netherlands

Location

Related Publications (4)

  • Chung EY, Palmer SC, Saglimbene VM, Craig JC, Tonelli M, Strippoli GF. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Cochrane Database Syst Rev. 2023 Feb 13;2(2):CD010590. doi: 10.1002/14651858.CD010590.pub3.

    PMID: 36791280DERIVED

  • Eisenga MF, Emans ME, van der Putten K, Cramer MJ, Diepenbroek A, Velthuis BK, Doevendans PA, Verhaar MC, Joles JA, Bakker SJL, Nolte IM, Braam B, Gaillard CAJM. Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease. J Am Heart Assoc. 2019 Aug 20;8(16):e011130. doi: 10.1161/JAHA.118.011130. Epub 2019 Aug 17.

    PMID: 31423921DERIVED

  • Emans ME, van der Putten K, Velthuis BK, de Vries JJ, Cramer MJ, America YG, Hillege HL, Meiss L, Doevendans PA, Braam B, Gaillard CA. Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging. BMC Cardiovasc Disord. 2012 Sep 18;12:76. doi: 10.1186/1471-2261-12-76.

    PMID: 22989293DERIVED

  • van der Putten K, Jie KE, Emans ME, Verhaar MC, Joles JA, Cramer MJ, Velthuis BK, Meiss L, Kraaijenhagen RJ, Doevendans PA, Braam B, Gaillard CA. Erythropoietin treatment in patients with combined heart and renal failure: objectives and design of the EPOCARES study. J Nephrol. 2010 Jul-Aug;23(4):363-8.

    PMID: 20383871DERIVED

MeSH Terms

Conditions

Heart FailureRenal Insufficiency, ChronicCardio-Renal Syndrome

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Branko Braam, MD, PhD

    UMC Utrecht, The Netherlands

    PRINCIPAL INVESTIGATOR

  • Carlo AJ Gaillard, MD, PhD

    Meander Medical Center Amersfoort, The Netherlands

    PRINCIPAL INVESTIGATOR

  • Pieter AF Doevendans, MD, PhD

    UMC Utrecht, The Netherlands

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

July 25, 2006

First Posted

July 26, 2006

Study Start

January 1, 2007

Primary Completion

July 1, 2011

Study Completion

July 1, 2011

Last Updated

December 2, 2011

Record last verified: 2011-11

Locations

NL(2)