Clinical Trial: Defibrotide in the Human Endotoxemia Model --‐ an Exploratory Trial Investigating the Effects and the Mechanisms of Defibrotide

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Defibrotide in the Human Endotoxemia Model -- an Exploratory Trial Investigating the Effects and the Mechanisms of Defibrotide

Brief Summary: Defibrotide is an anti-inflammatory and anti-coagulatory agent approved for treatment of veno-occlusive disease. Although it has been in clinical use for almost 30 years, the exact mechanism of action has never been fully elucidated. Thus, the effects of defibrotide will be investigated in the human endotoxemia model in order to gather further information on its actions.

Detailed Summary: Defibrotide (DF) is a highly complex polydisperse mixture of single-stranded phosphodiester oligodeoxyribonucleotides derived from the controlled depolymerization of porcine intestinal mucosal DNA. The entire mode of action remains unknown. Its actions may be summarized to pro-fibrinolytic, anti-inflammatory and anti-coagulatory actions. To better define the mechanisms of Defibrotide the effects of the substance will be investigated in the well-established endotoxemia model. Sixteen healthy volunteers will be randomized to receive LPS±defibrotide/placebo and four subjects will be randomized to receive Placebo± defibrotide/placebo in a single center, randomized, double blind, placebo controlled, two-way crossover trial. Immediately after a 2h infusion of 6,25mg/kg bodyweight defibrotide or placebo a LPS bolus of 2ng/kg bodyweight will be infused. Analyses will be performed by blood sampling at pre-defined time-points.
Sponsor: Bernd Jilma

Current Primary Outcome: Changes in prothrombin fragments f1+2 [ Time Frame: up to 24 hours ]

by elisa, the changes will be compared between the placebo and the verum phase within each subject


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Changes in coagulation specific biomarkers [ Time Frame: up to 24 hours ]
    Thrombin-Antithrombin Complexes
  • Changes in Fibrinolytic biomarkers [ Time Frame: up to 24 hours ]
    by elisa, D-Dimer, Plasmin-Antiplasmin Complexes
  • Inflammatory biomarkers [ Time Frame: up to 24 hours ]
    C-reactive Protein levels, Fibrinogen, TNF-alpha
  • changes in microparticle associated tissue factor activity [ Time Frame: up to 24 hours ]
    by elisa
  • Changes in Biomarkers of endothelial activation [ Time Frame: up to 24 hours ]
    by elisa, von-willebrand-factor, E-selectin,
  • Changes in Biomarkers of endothelial activation [ Time Frame: up to 24 hours ]
    Circulatin Endothelial cells by flow cytometry
  • Differential blood counts [ Time Frame: up to 24 hours ]
    by flow cytometry, incl. platelet counts, absolute and relative counts of leucocytes, erythrocytes, and leucocyte subpopulations
  • Blood pressure mmHg [ Time Frame: up to 24 hours ]
    safety parameters
  • Body Temperature degrees centigrade [ Time Frame: up to 24 hours ]
    safety parameters
  • Oxygen Saturation in percent [ Time Frame: up to 24 hours ]
    safety parameters
  • Heart rate in beats per minute [ Time Frame: up to 24 hours ]
    safety parameters


Original Secondary Outcome: Same as current

Information By: Medical University of Vienna

Dates:
Date Received: June 27, 2016
Date Started: April 2017
Date Completion: December 2017
Last Updated: March 22, 2017
Last Verified: March 2017