A PhaseⅡ, Randomized, Double-blind, Multi-center, Based On Standard Therapy, Placebo-controlled Study Of The Efficacy And Safety Of Recombinant Human Neurugulin-1βin Patients With Chronic Systolic Heart Failure

Background: Although important progress has been made for the therapy of heart failure in recent years, the mortality of the patient with heart failure is still high. From the Framinghan Study,the annual death rate of patient with NYHAⅡ～Ⅲwas 10%~25%, and 40%~50% for NYHAⅣ. So, the most important thing for us is to develop some more effective methords for the therapy of heart failure. As a cardiac cell differentiation factor, recombinant human Niulangelin-1β(rhNRG-1β) can directly bind to myocardial cells ErbB4 receptor, activate receptors and produce biological activity, preclinical trials have shown that rhNRG-1βcan repair damaged myocardial fiber structure, strengthen the link between myocardial cells and improve heart function, improve the survival rate of animals with heart failure. Rh NRG-1βmay have good prospects for clinical use.Objective: To investigate the efficacy and safety of recombinant human Neurugulin-1βin patients with chronic systolic heart failure.Method: After strict selection for patients with chronic heart failure from Mar. 2008 to Oct. 2008, 6 cases (5 males, 1 femals, age range 32~58 years, mean age 46.7 years) were enrolled, and all the patients received a randomized, double-blind, multi-center, based on standard therapy, placebo-controlled study. After 10 days administration of the drug, all the patients were respectively followed at the 11-13 day,30±5 day, 90±5 day,and were given a comprehensive assessment of the effectiveness and safety.Result: From the results of the major and minor observation indicators , we found that 3/4 of patients who received rhNRG-1βattained improving in 6MWT,MLHFQ,PRO-BNP,it was higher than the group with placebo(1/2). However, whether giving rhNRG-1βexcluding standerd heart failure drug therapy could obtain better result than placebo group, we still need multi-center datas for statistics and investigation because of so small sample size. About observation of safety, all of the 4 patients with rhNRG-1βcould complete the study with good tolerance, although 3 patiens got some mild reversible adverse events, there was no severe adverse events.Conclution: RhNRG-1βprovided a new pathway from the molecular to cell level for the chronic heart failure therapy. Our sub-center of the trend data shew that the patients with chronic systolic heart failure may have a therapeutic effect from rhNRG-1βwith no severe adverse events.