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
Runlin Gao, Jian Zhang, Liuquan Cheng, Xuesi Wu, Wei Dong, Xinchun Yang, Tianchang Li, Xifu Liu, Yabei Xu, Xinyan Li, Mingdong Zhou, Runlin Gao, Jian Zhang, Liuquan Cheng, Xuesi Wu, Wei Dong, Xinchun Yang, Tianchang Li, Xifu Liu, Yabei Xu, Xinyan Li, Mingdong Zhou
Abstract
Objectives: 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).
Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed