A phase I trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered low-anticoagulant heparin (M6229) in critically ill sepsis patients.

ABSTRACT:

Background

Histones released in response to cellular injury are important mediators of organ failure and death in sepsis. Preclinical studies demonstrate that neutralization of histones in sepsis is associated with improved outcome. M6229 is a low-anticoagulant heparin able to neutralize histones. We aimed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of M6229 in critically ill patients with sepsis.

Methods

This was a first-in-human, phase I, monocenter trial in patients with sepsis admitted to the intensive care unit (ICU). Patients received a single 6 h intravenous infusion of M6229. A modified continual reassessment method (mCRM) with escalation overdose control was used for dose-escalation. The model was based on the probability of activated

SUBMITTER: van Mourik N 

PROVIDER: S-EPMC12360993 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature