Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial.

Abstract

The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction. Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups. This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.