Rice-derived recombinant human serum albumin as an alternative to human plasma for patients with decompensated liver cirrhosis: a randomised, double-blind, positive-controlled and non-inferiority trial.

We sought to establish the safety and efficacy of OsrHSA, a recombinant HSA from bioengineered Oryza sativa (rice).

我们试图确立OsrHSA的安全性和有效性，OsrHSA是一种来自转基因水稻（Oryza sativa）的重组HSA。

Methods

In this multicentre, randomised, double-blindand positive-controlled study, patients with decompensated liver cirrhosis and serum albumin ≤30 g/L were recruited from 22 centres in China.

在这项多中心、随机、双盲和阳性对照研究中，招募了来自中国22个中心的失代偿性肝硬化患者，这些患者的血清白蛋白水平≤30 g/L。

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.

患者被随机分配到OsrHSA或pHSA（4:1）组，进行每日一次的静脉注射（10克或20克），直到他们的血清白蛋白水平达到35 g/L，最多持续2周，之后进行为期2周的随访。

The primary outcome was the proportion of patients to reach a serum albumin level of 35 g/L (non-inferiority margin <-0.20).

主要结果是达到血清白蛋白水平35 g/L的患者比例（非劣效性边界<-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).

在至少有一次基线后血清白蛋白值的接受研究药物的患者中评估结果（全分析集，FAS）。

Safety was evaluated in all patients who received the study drug.

所有接受研究药物的患者均进行了安全性评估。

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).

在2021年3月22日至2022年6月2日期间，共有220名患者接受了OsrHSA（n=175）或pHSA（n=45）治疗。其中216名患者被纳入全分析集（FAS），包括OsrHSA组171名患者和pHSA组45名患者。

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).

OsrHSA的主要结果（130/171，76%）与pHSA（34/45，75.6%）相当（差异=0.5%；97.5%置信区间的下限=-0.119）。

There was no significant difference between all secondary outcomes of OsrHSA and pHSA.

OsrHSA和pHSA的所有次要结果之间没有显著差异。

There were no drug-related serious adverse events.

未观察到与药物相关的严重不良事件。

Conclusions

Rice-derived HSA is non-inferior to plasma-derived HSA in efficacy and safety.

大米来源的人血清白蛋白在疗效和安全性上不劣于血浆来源的人血清白蛋白。

This finding should be confirmed in phase 3 trial.

这一发现应在III期临床试验中得到确认。

trial_registration_number

NCT04835480.

NCT04835480。