Chronic, Low Dose Erythropoetin Beta in Ischemic Cardiomyopathy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Ischemic Cardiomyopathy	Drug: erythropoetin beta Drug: placebo	Phase IV

MedlinePlus related topics:

Cardiomyopathy Heart Failure

ChemIDplus related topics:

Epoetin alfa Erythropoietin Epoetin beta

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

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)

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Change in global left ventricular ejection fraction between initial examination at study entry and the 6 months follow up examination employing cardiac MRI [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
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. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
35 I.E. kg/KG erythropoetin beta s.c. once per week for 6 months improves peak VO2 as measured by spiroergometry [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	May 2006
Estimated Study Completion Date:	February 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 35 I.E. erythropoetin beta given by subcutaneous injection once per week for 6 months.	Drug: erythropoetin beta 35 I.E. kg body weight subcutaneous once per week for 6 months
2: Placebo Comparator Placebo to erythropoetin beta.	Drug: placebo 35 I.E. kg body weight placebo to erythropoetin beta

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.

Eligibility

Ages Eligible for Study:	45 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00568542

Contacts


Contact: Martin W Bergmann, MD	49-309-401 ext 12916	martin.bergmann@charite.de

Contact: Heidrun Mehling, MD	49-309-417 ext 2221	heidrun.mehling@charite.de

Locations


Germany
	Charité Campus Buch	Recruiting
	Berlin, Germany, 13125
	Contact: Sibylle Schmidt, study nurse 49-9401 ext 12910 sibylle.schmidt@charite.de
	Contact: Angelika Weber, secretary 49-309-401 ext 52950 angelika-weber@helios-kliniken.de
	Sub-Investigator: Heidrun Mehling, MD
	Sub-Investigator: Jens Jordan, MD
	Charité Campus Virchow	Active, not recruiting
	Berlin, Germany, 13353

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators


Principal Investigator:	Martin W Bergmann, MD	Charité Camous Buch, University Medicine Berlin, Germany

More Information

Responsible Party:	Charité Campus Buch, University Medicine Berlin, Germany ( Priv.-Doz. Dr. Martin W. Bergmann )
Study ID Numbers:	8514077463, EudraCT number 2004-002646-35, EK 6 EA 3/015/05, KP-3910-4030711
First Received:	December 5, 2007
Last Updated:	May 7, 2008
ClinicalTrials.gov Identifier:	NCT00568542
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

cardiomyopathy

ischemia

percutaneous coronary intervention

remodeling

Study placed in the following topic categories:

Epoetin Alfa

Heart Failure

Heart Diseases

Ischemia

Cardiomyopathies

Additional relevant MeSH terms:

Pathologic Processes

Hematinics

Therapeutic Uses

Hematologic Agents

Cardiovascular Diseases

Pharmacologic Actions

ClinicalTrials.gov processed this record on August 29, 2008

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00568542