Phase 4
N=20
Defibrotide in the Human Endotoxemia Model --- an Exploratory Trial Investigating the Effects and the Mechanisms of Defibrotide
Healthy Volunteers · Endotoxemia
Bottom Line
View on ClinicalTrials.gov: NCT02876601 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
Dec 2019
Primary outcome: Primary: Prothrombin Fragments f1+2 — 31.1; 34.08; 27.41; 36.02 fold-change*h — p=0.408
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Defibrotide (Drug); Placebo (0.9% sodium chloride) (Drug); Lipopolysaccharide (Drug); Placebo (0.9% sodium chloride bolus) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bernd Jilma
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Prothrombin Fragments f1+2 |
31.1; 34.08; 27.41; 36.02 | 0.408 |
| SECONDARY Thrombin-Antithrombin Complexes |
23.39; 27.4; 17.46; 21.83 | 0.148 |
| SECONDARY Plasmin-Antiplasmin Complexes |
11.8; 9.99; 7; 7.12 | 0.039 sig |
| SECONDARY Tumor Necrosis Factor (TNF)-Alpha |
286; 326; 28.08; 21.01 | 0.642 |
| SECONDARY Tissue-type Plasminogen Activator |
21.8; 17; 20.57; 23.54 | 0.026 sig |
| SECONDARY Interleukin-6 |
1543; 1144; 35; 31 | 0.326 |
| SECONDARY E-Selectin |
35; 33; 21; 41 | 0.796 |
| SECONDARY Plasminogen Activator Inhibitor 1 |
216; 477; 25; 24.86 | 0.918 |
| SECONDARY Von Willebrand Factor Antigen |
54; 53; 27; 26 | 0.877 |
| SECONDARY Clotting Time in Thromboelastometry |
1.12; 1.12; -0.2; 2.14 | 0.423 |
| SECONDARY Maximum Lysis in Thromboelastometry |
7.9; 7.7; 6.84; 6.85 | 0.938 |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02876601). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.