• Xiao-Yun Hu, Weiwen Zhang, Difen Wang, Yunbo Sun, Zhenjie Hu, Bin Zang, Yongwen Feng, Huaxue Wang, Jianxin Zhou, Qian Zhao, Hongzhong Liu, Teng Wang, Wei Jiang, Chun-Yao Wang, Chunyan Jin, Kai Dong, Shuai Chen, Xiaoqing Yao, Pei Hu, Bin Du, and China Critical Care Clinical Trials Group (CCCCTG).
• Medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Beijing 100730, China; State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, 1 Shuai Fu Yuan, Beijing 100730, China.
• J Crit Care. 2023 Aug 1; 76: 154294154294.

PurposeTo evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure.Materials And MethodsThis was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters.ResultsOf 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days.ConclusionsIn patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted.Trial Registrationhttp://ClinicalTrials.gov, NCT03237728.Copyright © 2023. Published by Elsevier Inc.

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