Clinical Study On Absorbable Macroporous Polysaccharide Composites As Hemostatic Agents For Intraoperative Bleeding

Chitosan and its derivatives based formulations have been used for topical hemostasis for decades.However,the number of randomized control trials about carboxymethyl-chitosan-based hemostatic agents is limited.Absorbable macroporous polysaccharide composites(AMPC)is mainly composed of carboxymethyl-chitosan and used as hemostatic agents.This study is an exploratory,non-inferiority and randomized controlled clinical study.The aim of this study is to compare the effectiveness and safety of AMPC with compound microporous polysaccharide haemostatic powder(CMPHP)(2:1 ratio)for treatment of intraoperative bleeding in thyroid,breast,hepatic and gastrointestinal surgery.From May 2018 to March 2021,290 patients were recruited,while 38 of them were excluded.A total of 252 participants were randomized.Randomized and treated participants in AMPC and CMPHP groups were 166 and 84,respectively.And two randomized participants didn’t use AMPC or CMP HP.The main results are as follows:(1)The primary efficacy endpoint(rate of hemostasis within 300 seconds)was 98.8%(163 of 165)in AMPC and 94.0%(78 of 83)in CMPHP.The two-sided 95%confidence interval of the difference of the primary efficacy endpoint(-0.57%,10.20%)was upper the pre-specified non-inferiority limit of-10%.The null hypothesis was thus rejected(t-test,P<0.001).Treatment with AMPC was therefore considered to be not inferior to treatment with CMPHP at a significance level of 0.05(two-sided).(2)The secondary efficacy endpoint(hemostasis time)showed no statistically significant difference between the groups(P>0.05).However,hemostasis time(median[interquartile range])with AMPC(87[52,180]seconds)was lower than CMPHP(106[55,181]seconds).(3)Safety endpoint,including laboratory inspection and adverse events,appeared no significant difference between two groups.Changes in laboratory parameters over time and shifts to abnormal values were typical of four operations and similar between two groups at all follow-up points.No noticeable adverse effects associated with AMPC or CMPHP were observed.AMPC is well tolerated as topical hemostatic agents,non-inferior to CMPHP and possesses good biocompatibility.As an integral part to translational medicine of AMPC,the clinical study not only fuels novel topical hemostatic agents development and commercialization,but also make up for the deficiency of the biomedical absorbable hemostatic agents in China.