Intramyocardial injections of erythropoietin-analogue C.E.R.A. in ischemic cardiomyopathy: the ALSTER C.E.R.A. trial

Objectives: Erythropoietin (EPO) improved cardiac regeneration in experimental models of ischemic heart disease. A pilot trial found subcutaneously administered EPO to improve surrogate markers of left ventricular (LV) function in ischemic cardiomyopathy. This clinical study tests the feasibility and safety of the intramyocardial delivery route of a long-acting EPO-analogue (C.E.R.A.) in patients with ischemic cardiomyopathy. Methods: The ALSTER C.E.R.A. trial was a Phase II, open label, 1:1 randomized, single-center study testing intramyocardial injections of long-acting EPO analogue C.E.R.A. (C.E.R.A. NOGA: once 180 µg) using the NOGA XP system versus the subcutaneous application (C.E.R.A. SC: 30µg s.c./month for 6 months) in 59 symptomatic chronic heart failure (HF) patients with impaired LV function (ejection fraction (EF) £ 45%). Results: Follow-up up to three years with both clinical and imaging endpoints found intramyocardial delivery of C.E.R.A. to be feasible, safe and to possibly attenuate LV remodeling. Patients in the C.E.R.A. NOGA group showed stable parameter for LV end-diastolic diameter and volume (LVEDD and LVEDV), while C.E.R.A. SC patients had significant dilation of the LV (C.E.R.A. NOGA vs. SC, mean ± standard error of the mean: DLVEDD 0.02±0.1mm, p=0.8 vs. 0.3±0.09mm, p=0.0026; DLVEDV 10±15.9ml, p=0.5 vs. 34.8±11.3ml, p=0.0081; ∆EF 2.4±1.2%, p=0.045 vs. -1.6±1.1, p=0.1 respectively). NYHA class significantly improved and the hospitalization rate was numerically reduced in the C.E.R.A. NOGA group, while three-year mortality was identical. Conclusions: Intramyocardial injection of C.E.R.A. is feasible, safe and possibly attenuates LV remodeling in ischemic HF patients with LV dysfunction compared to the systemic application.