Chronic, Low Dose Erythropoetin Beta in Ischemic Cardiomyopathy

Ischemic Cardiomyopathy Clinical Trial

— EPOHeart  

Official title:

Pilot Study to Assess the Effect of Low Dose Epoetin Beta Administered for Six Month in Patients With Ischemic Heart Failure Subjected to Percutaneous Coronary Intervention (PCI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00568542
• Other study ID #: 8514077463
• Secondary ID: EudraCT number 2
• Status: Completed
• Phase: Phase 4
• First received: December 5, 2007
• Last updated: August 3, 2009
• Start date: May 2006
• Est. completion date: October 2008

Study information

• Verified date: August 2009
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The study is testing the hypothesis, that the application of low dose erythropoetin beta (35 I.E./kg BW/week) for 6 months following successful coronary revascularization by PCI improves left ventricular remodeling as assessed by cardiac MRI.

Description:

Several effects known to be exerted by erythropoetin (EPO) directly in the heart independent of hemoglobin levels could be of value immediately after revascularization procedures in ischemic cardiac remodeling: the generation of new capillaries is enhanced by the mobilization of endothelial progenitor cells from the bone marrow. EPO is neuron- and cardio-protective after ischemia/reperfusion. Administration of EPO enhances neuronal progenitors to differentiate into functional neurons; this observation may also be valid for the cardiac compartment. The concept of organ-specific effects of EPO independent of hemoglobin levels is supported by the analysis of EPO analogues lacking hematopoietic activity. In humans, currently this concept can only be tested by the use of EPO-doses that do not affect hemoglobin levels. The concept is valid as clinical trials have been performed showing that doses as low as 5000 I.U. EPO once weekly increase the levels of endothelial progenitor cells in blood. On the other hand, recent clinical trials have also shown neutral or even deleterious effects of high dose EPO treatment raising hemoglobin levels to above 12mg/dl in pre-dialysis patients concerning cardiovascular endpoints. Therefore, the chronic, hemoglobin-neutral administration of low doses of EPO might be a successful approach concerning ischemic cardiomyopathy.

Study outline:

This investigator initiated, double-blind, placebo-controlled study is testing the hypothesis, that low doses of erythropoietin beta (35 I.U./kg body weight) started within 14 days after a successful percutaneous coronary intervention enhance left ventricular remodeling as determined by comparison of two cardiac MRI´s over a course of 6 months. Secondary endpoints include changes in diastolic dysfunction as measured by echocardiography, VO2 measured by spiroergometry and serum brain natriuretic peptide levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 75 Years

Eligibility

Inclusion Criteria:

• successful coronary intervention < 14 days

• regional contraction deficit of the left ventricle as detected either by echocardiography or cardiacMRI

• globally reduced ejection fraction (cardiac MRI or echocardiography: < 60%)

• willing and able to cooperate

• voluntary participation

Exclusion Criteria:

• contraindication for cardiac MRI (i.e. pacemaker, ICD current or within the next 6 months, other metal implants)

• cardiogenic shock at time of inclusion

• uncontrolled hypertension (systolic blood pressure > 180mmHg)

• hemoglobin > 16mg/dl

• thrombocytosis

• malignant tumor

• missing informed consent

• renal failure (creatinine > 300 mg/dl)

• liver failure

• other prognosis limiting, severe diseases (i.e. dementia)

• indication for open label erythropoietin treatment

• allergy towards solvents of the EPO preparation

• woman of childbearing potential

• other clinical study within the preceding 30days

• known alcohol or drug abuse

• neurologic or psychiatry disorders

• previous organ transplantation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Ischemia
• Ischemic Cardiomyopathy

Intervention

Drug:
• erythropoetin beta
35 I.E. kg body weight subcutaneous once per week for 6 months
• placebo
35 I.E. kg body weight placebo to erythropoetin beta

Locations

Country	Name	City	State
Germany	Charité Campus Buch	Berlin
Germany	Charité Campus Virchow	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in global left ventricular ejection fraction between initial examination at study entry and the 6 months follow up examination employing cardiac MRI		6 months	No
Secondary	The application of 35 I.E./kg body weight erythropoetin beta s.c. once per week for 6 months is well tolerated and safe in patients after PCI.		6 months	Yes
Secondary	35 I.E. kg/KG erythropoetin beta s.c. once per week for 6 months improves left ventricular regional wall motion as assessed by cardiac MRI.		6 months	No
Secondary	35 I.E. kg/KG erythropoetin beta s.c. once per week for 6 months reduces serum levels of brain natriuretic peptide as a measure of heart failure.		6 months	No
Secondary	35 I.E. kg/KG erythropoetin beta s.c. once per week for 6 months improves peak VO2 as measured by spiroergometry		6 months	No
Secondary	35 I.E. kg/KG erythropoetin beta s.c. once per week for 6 months improves measures or cardiac diastolic dysfunction as assessed by echocardiography		6 months	No
Secondary	35 I.E. kg/KG erythropoetin beta s.c. once per week for 6 months improves cardiac tissue texture aqs assessed by contrast-enhanced cardiac MRI		6 months	No