NCT04861922

Unfractioned Heparin for Treatment of Sepsis Caused by Abdominal Infection

Status unknown Phase 3 Last updated 21 March 2023

What this trial tests

Phase 3 trial testing Unfractionated Heparin in Sepsis in 100 participants. Status unknown.

Timeline

11 May 2021

Primary endpoint
30 December 2023

30 July 2024

Quick facts

Lead sponsor	The Third Xiangya Hospital of Central South University
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	100
Start date	11 May 2021
Primary completion	30 December 2023
Estimated completion	30 July 2024
Sites	1 location across China

Drugs / interventions tested

• Unfractionated Heparin — full drug profile →

Conditions studied

• Sepsis — all drugs for Sepsis →
• Gram-Negative Bacterial Infections — all drugs for Gram-Negative Bacterial Infections →
• Heparin — all drugs for Heparin →

Sponsor

The Third Xiangya Hospital of Central South University

Who can join

Adults 18 to 75, any sex, with Sepsis or Gram-Negative Bacterial Infections. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Sepsis is the leading cause of death in intensive care units and a major public health concern in the world. Heparin, a widely used anticoagulant medicine to prevent or treat thrombotic disorders, has been demonstrated to prevent organ damage and lethality in experimental sepsis models. However, the efficacy of heparin in the treatment of clinical sepsis is not consistent. Caspase-11, a cytosolic receptor of LPS, triggers lethal immune responses in sepsis. Recently, we have revealed that heparin prevents cytosolic delivery of LPS and caspase-11 activation in sepsis through inhibiting the heparanase-mediated glycocalyx degradation and the HMGB1- LPS interaction, which is independent of its anticoagulant properties. In our study, it is found that heparin treatment could prevent lethal responses in endotoxemia or Gram-negative sepsis, while caspase-11 deficiency or heparin treatment failed to confer protection against sepsis caused by Staphylococcus aureus, a type of Gram-positive bacterium. It is probably that other pathogens such as Gram-positive bacteria might cause death through mechanisms distinct from that of Gram-negative bacteria. Peptidoglycan, a cell-wall component of Gram-positive bacteria, can cause DIC and impair survival in primates by activating both extrinsic and intrinsic coagulation pathways, which might not be targeted by heparin. We speculate that the discrepancy between the previous clinical trials of heparin might be due to the difference in infected pathogens. Thus, stratification of patients based on the type of invading pathogens might improve the therapeutic efficiency of heparin in sepsis, and this merits future investigations.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Heparan sulfates and heparan sulfate binding proteins in sepsis.
   Liao YE, Liu J, Arnold K. · · 2023 · cited 15× · PMID 36865384 · DOI 10.3389/fmolb.2023.1146685
2. The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.
   Jiang H, Guo Y, Wang Q, Wang Y, et al · · 2024 · cited 5× · PMID 39445002 · DOI 10.1002/mco2.785
3. When glycobiology meets inflammasome activation: Insights and implications.
   Zhang H, Jin T, Xue M, Wu S, et al · · 2026 · PMID 40194699 · DOI 10.1016/j.jare.2025.03.054