Hamshere Stephen, Arnous Samer, Choudhury Tawfiq, Choudry Fizzah, Mozid Abdul, Yeo Chia, Barrett Catherine, Saunders Natalie, Gulati Ankur, Knight Charles, Locca Didier, Davies Ceri, Cowie Martin R, Prasad Sanjay, Parmar Mahesh, Agrawal Samir, Jones Daniel, Martin John, McKenna William, Mathur Anthony
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK.
Eur Heart J. 2015 Nov 21;36(44):3061-9. doi: 10.1093/eurheartj/ehv390. Epub 2015 Sep 2.
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.
REGENERATE - DCM试验是首个II期随机、安慰剂对照试验，旨在评估给予粒细胞集落刺激因子（G - CSF）联合或不联合冠状动脉内（IC）注射自体骨髓来源细胞（BMC）是否能改善扩张型心肌病（DCM）伴严重心功能不全患者的左心室（LV）整体功能。
60例DCM患者，转诊时左心室射血分数（LVEF）≤45%，纽约心脏协会（NYHA）分级≥2且无心肌病继发原因，被平均随机分为四组：外周安慰剂（生理盐水）组、外周G - CSF组、外周G - CSF联合IC血清组以及外周G - CSF联合IC BMC组。除外周安慰剂组外，所有患者均接受5天的G - CSF治疗。在IC治疗组中，于第6天进行骨髓采集并IC注入细胞或血清。主要终点为从基线至3个月时LVEF的变化，通过先进的心脏成像测定。3个月时，外周G - CSF联合IC BMC治疗使LVEF提高了5.37个百分点（从32.93%±16.46升至38.30%±12.97，P = 0.0138），且这种改善持续至1年。这与NYHA分级降低、NT - pro BNP降低、运动能力和生活质量改善相关。其余治疗组的LVEF未见显著变化。
这是首个采用G - CSF与IC细胞治疗新组合的随机、安慰剂对照试验，证明该治疗可改善DCM患者的心脏功能、症状及生化指标。
