Effect of allogeneic adipose tissue derived mesenchymal stromal cell treatment in chronic ischemic heart failure with reduced ejection fraction – The SCIENCE Trial

Background and Aims The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischemic heart failure with reduced ejection fraction (HFrEF). Methods The study was a European multi-centre double-blinded placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were NYHA II-III, left ventricular ejection fraction (LVEF) < 45%, and NT-ProBNP levels>300 pg/mL. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. Primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6 months follow up measured by echocardiography. Results A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac related adverse events during a 3-years follow-up period. There were no significant differences between the groups during follow up in LVESV (0.3 ± 5.0 ml, P = 0.945), nor in secondary endpoints left ventricular end-diastolic volume (−2.0 ± 6.0 ml, P = 0.736) and LVEF (−1.6 ± 1.0%, P = 0.119). The NYHA classification improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-Minute Walk Test, NT-ProBNP, CRP or quality-of-life the first year in any of the two groups. Conclusion The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the predefined endpoints and induce restoration of cardiac function or clinical symptoms
Aims The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF). Methods and results The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II–III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (−2.0 ± 6.0 ml, p = 0.736) and LVEF (−1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups. Conclusion The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.