Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial.

Abstract

PURPOSE:

To 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 METHODS:

This 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.

RESULTS:

Of 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.

CONCLUSIONS:

In patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted.

TRIAL REGISTRATION:

http://ClinicalTrials.gov, NCT03237728.

• Authors: 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, China Critical Care Clinical Trials Group (CCCCTG)
• Journal: Journal of critical care (J Crit Care) Vol. 76 Pg. 154294 (08 2023) ISSN: 1557-8615 [Electronic] United States
• PMID: 37116228 (Publication Type: Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• kukoamine B
• Caffeic Acids
• Spermine
• Vasoconstrictor Agents

Topics

• Humans
• Sepsis (drug therapy)
• Caffeic Acids (therapeutic use)
• Spermine (therapeutic use)
• Vasoconstrictor Agents (therapeutic use)
• Double-Blind Method
• Treatment Outcome