Skip to main content
OpenTrials
Completed

NCT Number: NCT02876601

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy Volunteers Bacteremia Cardiovascular Diseases Embolism and Thrombosis Endotoxemia Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Systemic Inflammatory Response Syndrome Thrombosis Toxemia Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, 1090, Austria

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • >18 years of age
  • <90kg body weight
  • Normal findings in medical history and physical examination unless the investigator considers the abnormality to be clinically irrelevant
  • Normal laboratory values unless the investigator considers abnormalities to be clinically irrelevant
  • Ability to understand the purpose and nature of the study, as well as the associated risks

Exclusion criteria

  • Intake of any drugs that may interfere with the trial's endpoints or drugs (i.e. platelet inhibitors, anticoagulants, etc.)
  • Positive results of HIV or hepatitis virology
  • Acute illness with systemic inflammatory reactions
  • Known allergies, hypersensitivities or intolerances to any of the used substances
  • Acute or recent bleeding episodes, increased risk of bleeding at the discretion of the investigator
  • Participation in an LPS trial within 6 weeks of the first study day
  • Pregnancy or breastfeeding

Treatment and study plan

Defibrotide

Drug

6.25mg/kg bodyweight over 2h infusion

Placebo (0.9% Sodium Chloride)

Drug

(0.9% sodium chloride) infusion over 2h infusion

lipopolysaccharide

Drug

bolus infusion of 2ng/kg bodyweight lps

Placebo (0.9% sodium chloride bolus)

Drug

(0.9% sodium chloride) bolus infusion

Primary outcomes

  1. Prothrombin Fragments f1+2

    Time frame: The parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold*h.

    The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison

Secondary outcomes

  1. Thrombin-Antithrombin Complexes

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold*h.

    The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison

  2. Plasmin-Antiplasmin Complexes

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, and 6h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold*h.

    The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison

  3. Tumor Necrosis Factor (TNF)-Alpha

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject.

    The respective arbitrary unit therefore is fold*h.

  4. Tissue-type Plasminogen Activator

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject.

    The respective arbitrary unit therefore is fold*h.

  5. Interleukin-6

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold*h.

  6. E-Selectin

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject.

    The respective arbitrary unit therefore is fold*h.

  7. Plasminogen Activator Inhibitor 1

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject.

    The respective arbitrary unit therefore is fold*h.

  8. Von Willebrand Factor Antigen

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The quantification of von Willebrand Factor is based on reference values and results are in % of "normal".

    The respective arbitrary unit therefore is %*h.

  9. Clotting Time in Thromboelastometry

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.

    In this analysis, first of all a ratio of the measurement time point to the baseline was calculated. Thereafter deltas (baeline-ratio) were calculated. With the results an AUC was calculated.

    The respective arbitrary unit therefore is fold*h.

  10. Maximum Lysis in Thromboelastometry

    Time frame: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h and AUC was calculated based on these measurements.

    Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject.

    The respective arbitrary unit therefore is fold*h.

Sponsors and collaborators

Lead sponsor

Bernd Jilma

Other

Registry information

Official study title

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

Acronym: LPS_DF

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Aug 24, 2016
Registry last updated
Dec 19, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.