Chronic, Low Dose Erythropoetin Beta in Ischemic Cardiomyopathy (EPOHeart)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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)|
- 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 ]
- 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 ]
|Study Start Date:||May 2006|
|Study Completion Date:||October 2008|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 1
35 I.E. erythropoetin beta given by subcutaneous injection once per week for 6 months. The drug is self-administered.
Drug: erythropoetin beta
35 I.E. kg body weight subcutaneous once per week for 6 months
Other Name: NeoRecormom 10.000 I.E. Patronen Zul.Nr. EU/1/97/031/021-022
Placebo Comparator: 2
Placebo to erythropoetin beta.
35 I.E. kg body weight placebo to erythropoetin beta
Other Name: Placebo to NeoRecormon 10.000 patron
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.
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.
|Charité Campus Buch|
|Berlin, Germany, 13125|
|Charité Campus Virchow|
|Berlin, Germany, 13353|
|Principal Investigator:||Martin W Bergmann, MD||Charité Camous Buch, University Medicine Berlin, Germany|