Document resource
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.