A Phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure.
OBJECTIVE
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.


BACKGROUND
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%).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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).
Gao
Runlin
R
Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Zhang
Jian
J
Cheng
Liuquan
L
Wu
Xuesi
X
Dong
Wei
W
Yang
Xinchun
X
Li
Tianchang
T
Liu
Xifu
X
Xu
Yabei
Y
Li
Xinyan
X
Zhou
Mingdong
M
D000328:Adult; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D020890:Neuregulin-1; D011994:Recombinant Proteins