Article
作者: Qin, Zhijie ; Yao, Lvfeng ; Zhou, Zhongyin ; Mao, Xiaorong ; Li, Guang-Ming ; Yu, Zujiang ; Wang, Fengmei ; Shang, Jia ; Wu, Cuisong ; Yang, Jinhui ; Wang, Xinrui ; Yang, Daichang ; Lu, Xiaobo ; Lin, Bingliang ; Chen, Yue ; Li, Xing ; Zhang, Jiming ; Jia, Ji-Dong ; Yang, Cliff Y ; Wang, Guiqiang ; Zhang, Zong ; Yang, Yida ; Wu, Xiaofeng ; Gu, Ye ; Ma, Hongyan ; Gao, Yanhang ; Hu, Zhongjie ; Niu, Junqi ; Wang, Lichun
BACKGROUND:Despite inadequate supply and potential contamination risk, human plasma has remained the only source for human serum albumin (pHSA) intravenous administration since the 1940s.
OBJECTIVE:We sought to establish the safety and efficacy of OsrHSA, a recombinant HSA from bioengineered Oryza sativa (rice).
DESIGN:In this multicentre, randomised, double-blind and positive-controlled study, patients with decompensated liver cirrhosis and serum albumin ≤30 g/L were recruited from 22 centres in China. The patients were randomly assigned to OsrHSA or pHSA (4:1) to once-daily intravenous injection (10 g or 20 g) until their serum albumin level reached 35 g/L, for a maximum of 2 weeks, with 2 weeks of follow-up. The primary outcome was the proportion of patients to reach a serum albumin level of 35 g/L (non-inferiority margin <-0.20). Outcomes were evaluated in patients who received the study drug and had at least one post-baseline serum albumin value (full analysis set, FAS). Safety was evaluated in all patients who received the study drug.
RESULTS:Between 22 March 2021 and 2 June 2022, 220 patients received OsrHSA (n=175) or pHSA (n=45). 216 patients were included in the FAS (OsrHSA, n=171; pHSA, n=45). Primary outcome of OsrHSA (130/171, 76%) was non-inferior to pHSA (34/45, 75.6%) (difference=0.5%; lower limit of 97.5% CI=-0.119). There was no significant difference between all secondary outcomes of OsrHSA and pHSA. There were no drug-related serious adverse events.
CONCLUSIONS:Rice-derived HSA is non-inferior to plasma-derived HSA in efficacy and safety. This finding should be confirmed in phase 3 trial.
TRIAL REGISTRATION NUMBER:NCT04835480.