Chronic, Low Dose Erythropoetin Beta in Ischemic Cardiomyopathy

NCT ID: NCT00568542

Last Updated: 2009-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2008-10-31

Brief 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.

Detailed 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.

Conditions

Ischemic Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

35 I.E. erythropoetin beta given by subcutaneous injection once per week for 6 months. The drug is self-administered.

Group Type: ACTIVE_COMPARATOR

erythropoetin beta

Intervention Type: DRUG

35 I.E. kg body weight subcutaneous once per week for 6 months

2

Placebo to erythropoetin beta.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

35 I.E. kg body weight placebo to erythropoetin beta

Interventions

erythropoetin beta

35 I.E. kg body weight subcutaneous once per week for 6 months

Intervention Type: DRUG

placebo

35 I.E. kg body weight placebo to erythropoetin beta

Intervention Type: DRUG

Other Intervention Names

NeoRecormom 10.000 I.E. Patronen Zul.Nr. EU/1/97/031/021-022; Placebo to NeoRecormon 10.000 patron

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Charité Campus Buch, University Medicine Berlin, Germany

Principal Investigators

Martin W Bergmann, MD

Role: PRINCIPAL_INVESTIGATOR

Charité Camous Buch, University Medicine Berlin, Germany

Locations

Charité Campus Buch

Berlin, , Germany

Charité Campus Virchow

Berlin, , Germany

Countries

Germany

References

Bergmann MW, Haufe S, von Knobelsdorff-Brenkenhoff F, Mehling H, Wassmuth R, Munch I, Busjahn A, Schulz-Menger J, Jordan J, Luft FC, Dietz R. A pilot study of chronic, low-dose epoetin-beta following percutaneous coronary intervention suggests safety, feasibility, and efficacy in patients with symptomatic ischaemic heart failure. Eur J Heart Fail. 2011 May;13(5):560-8. doi: 10.1093/eurjhf/hfr002.

Reference Type: DERIVED

PMID: 21505058 (View on PubMed)

Other Identifiers

EudraCT number 2004-002646-35

Identifier Type: -

Identifier Source: secondary_id

EK 6 EA 3/015/05

Identifier Type: -

Identifier Source: secondary_id

KP-3910-4030711

Identifier Type: -

Identifier Source: secondary_id

8514077463

Identifier Type: -

Identifier Source: org_study_id