An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial.

AIMS: The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function.

METHODS AND RESULTS: Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons.

CONCLUSION: We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.