Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
J Am Coll Cardiol. 2010 May 4;55(18):1907-14. doi: 10.1016/j.jacc.2009.12.044.
The purpose of this study was to assess the safety and efficacy of recombinant human neuregulin-1 (rhNRG-1) in chronic heart failure (CHF) patients.
Neuregulin-1 plays important roles in maintaining cardiomyocyte structure and cardiac pumping functionality and physiology. Previously, rhNRG-1 was proven to be effective in treating heart failure in animals by reducing end-diastolic volume (EDV) and end-systolic volume (ESV) and increasing left ventricular ejection fraction (LVEF%).
A total of 44 CHF patients designated as New York Heart Association functional class II or III were enrolled in a double-blind, randomized manner and treated with a placebo or rhNRG-1 (0.3, 0.6, or 1.2 microg/kg/day) for 10 days, in addition to standard therapies. The follow-up period was 90 days; left ventricular function and structure measured by magnetic resonance imaging were the primary end points.
Although not statistically different from placebo, the LVEF% was significantly increased by 27.11 +/- 31.12% (p = 0.009) at day 30 after rhNRG-1 treatment in the 0.6-microg/kg group, whereas it was only increased 5.83 +/- 25.75% in the placebo group (p = 0.49). In addition, there were decreases in ESV (-11.58 +/- 12.74%, p = 0.002) and EDV (-5.64 +/- 10.03%, p = 0.05) in the 0.6-microg/kg/day group at day 30; more importantly, both ESV and EDV levels continued to decrease at day 90 (-20.79 +/- 17.03% and -14.03 +/- 13.17%, respectively), accompanied by a sustained increase in LVEF%. This suggests that short-term treatment with rhNRG-1 results in a long-term reversal of remodeling. The effective dose was proven to be tolerable and safe for CHF patients.
rhNRG-1 improved the cardiac function of CHF patients by increasing the LVEF% and showed the capability of antiremodeling by decreasing ESV and EDV compared with pre-treatment. (A Randomized, Double-Blind, Multi-Center, Placebo Parallel controlled, Standard Therapy Based Phase II Clinical Trial to Evaluate the Efficacy and Safety of Recombinant Human Neuregulin-1 for Injection in Patients with Chronic Heart Failure; ChiCTR-TRC-00000414).
本研究旨在评估重组人神经调节蛋白-1（rhNRG-1）在慢性心力衰竭（CHF）患者中的安全性和疗效。
神经调节蛋白-1在维持心肌细胞结构和心脏泵功能和生理方面发挥着重要作用。先前的研究表明，rhNRG-1 通过降低舒张末期容积（EDV）和收缩末期容积（ESV）以及增加左心室射血分数（LVEF%），在动物心力衰竭治疗中具有疗效。
共纳入 44 名纽约心脏协会功能 II 或 III 级的 CHF 患者，采用双盲、随机方式接受安慰剂或 rhNRG-1（0.3、0.6 或 1.2μg/kg/天）治疗 10 天，同时接受标准治疗。随访期为 90 天；主要终点为磁共振成像测量的左心室功能和结构。
rhNRG-1 治疗 30 天后，0.6μg/kg 组的 LVEF% 较安慰剂组显著增加 27.11±31.12%（p=0.009），而安慰剂组仅增加 5.83±25.75%（p=0.49）。此外，0.6μg/kg/天组在 30 天时 ESV（-11.58±12.74%，p=0.002）和 EDV（-5.64±10.03%，p=0.05）降低；更重要的是，ESV 和 EDV 水平在 90 天时持续降低（分别为-20.79±17.03%和-14.03±13.17%），同时 LVEF% 持续升高，提示 rhNRG-1 短期治疗可导致长期重构逆转。有效剂量对 CHF 患者是耐受且安全的。
rhNRG-1 通过增加 LVEF% 改善 CHF 患者的心功能，并通过降低 ESV 和 EDV 显示出抗重构的能力，与治疗前相比。（一项基于标准治疗的注射用重组人神经调节蛋白-1治疗慢性心力衰竭患者的有效性和安全性的随机、双盲、多中心、安慰剂平行对照、Ⅱ期临床试验；ChiCTR-TRC-00000414）
