Heart failure
Conditions
Interventions
Intervention:
Treatment with rHu-EPO (NeoRecormon®, Roche), administered subcutaneously once
weekly.
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: -Male and female patients >= 18 years of age. -Congestive heart failure, NYHA II-IV based on complaints of the patient at randomization, and a documented ejection fraction 11 µmol/L ; ferritin = 3 months: no addition or deletion of any new drug(s) to treat heart failure (dose changes will be allowed); and no hospitalization for heart failure >= 3 months prior to randomization. -Written, informed consent.
Exclusion criteria
Exclusion criteria: -Known hypersensitivity to NeoRecormon or any of its components. -Female patients of childbearing age not using an adequate method of contraception. -Pregnancy. -Participation in an Investigational Drug Trial in the last 6 months before randomization. -Known non-CHF-related cause of anemia (additional internal medicine evaluation required, see later) including carcinoma, gastrointestinal bleeding focus, bone marrow dysfunction (for example anaplastic anemia), hypothyroidism, vitamin B12 deficiency, iron deficiency, folic acid depletion. -Severe renal dysfunction, creatinin clearance 220 mmol/L (possible or definite renal indication for exogenous EPO administration). -Scheduled revascularization procedures (PTCA, CABG) or CRT (cardiac resynchronization therapy), known at trial entry. -Any other foreseeable indication for surgery within the trial period. -Severe COPD (FEV1140/90 mmHg). -Patients with a history of venous thrombo-embolic disease, including deep venous thrombosis and pulmonary embolism. -CHF-patients not clinically stable, i.e. addition or deletion of any new drug(s) to treat heart failure (dose changes will be allowed) or hospitalization for heart failure >= 3 months prior to randomization. -Patients with a myocardial infarction or cerebrovascular accident within 6 months before randomization. -Contraindication for MRI (implant devices, claustrophobia) -Curable malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main study parameters/endpoints: Myocardial perfusion and myocardial metabolism/efficiency. | — |
Secondary
| Measure | Time frame |
|---|---|
| State-of-the-art CMR techniques will be used to assess the treatment-related changes in left ventricular (LV) ejection fraction, a measure of global cardiac function. In addition, cardiac dimensions, intramural regional systolic and diastolic (relaxation) myocardial function in conjunction with strain analysis and quantification of torsion and untwisting, as well as myocardial fibrosis will be assessed as secondary efficacy measures. Measurement of parameters related to reversed remodeling as determined by CMR: Reversed ventricular remodeling: will be defined as a decrease of LV end-systolic volume > 10% of baseline value. Echocardiography of left and right ventricular function: Transthoracic echocardiography: will be performed at baseline and at 6, 12 and 18 months follow-up for assessment of left ventricular (LV) dimensions and function. The LV systolic function will be assessed using Simpson*s rule in the apical two- and four-chamber views. The LV diastolic function is assessed by the E/A-ratio and TDI of the Mitral valve annulus. Right ventricular function is assessed by measuring the TAPSE (Tricuspid Annular Peak Systolic Excursion) and TDI of the Tricuspid annulus. Image post-processing will be performed on site. (see appendix 10) Change of functional New York Heart Association (NYHA) class for heart failure; Change of quality of life (Minnesota life questionnaire, see appendix 2), and cognitive function assessment (Hodkinson Abbreviated Mental Test, (see appendix 5). 6-minute walk test and VO2max; Six minute walk test: the distance in meters walked during 6 minutes with normal pace on a standard trajectory (see Appendix 3). VO2max will be measured using a bicycle ergometer with the Naughton protocol (see Appendix 6). CEUS-test: microvascular function test of skin- and skeletal muscle tissue (see Appendix 14). Biomarkers: NT-proBNP, Cystatine C, TNFa, VEGF. Physical examination: includes length, body weight, blood pressure, heart r | — |
Countries
Netherlands
Outcome results
None listed