1. Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial.
- Author
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Hu XY, Zhang W, Wang D, Sun Y, Hu Z, Zang B, Feng Y, Wang H, Zhou J, Zhao Q, Liu H, Wang T, Jiang W, Wang CY, Jin C, Dong K, Chen S, Yao X, Hu P, and Du B
- Subjects
- Humans, Caffeic Acids therapeutic use, Spermine therapeutic use, Vasoconstrictor Agents therapeutic use, Double-Blind Method, Treatment Outcome, Sepsis drug therapy
- 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., Competing Interests: Declaration of Competing Interest All authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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