MedDataX Logo

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

NCT ID: NCT02876601

Last Updated: 2019-12-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-18

Study Completion Date

2018-02-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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 Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy Volunteers Endotoxemia

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Coagulation Inflammation Defibrotide Fibrinolysis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Subjects will be randomized to receive LPS (n=16) or placebo (n=4) first. In each group they will undergo two study periods (crossover trial): a placebo period and a defibrotide period. The placebo group (n=4) will only be analyzed descriptively.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Defibrotide/LPS

2ng/kg lipopolysaccharide period I: 6.25mg/kg bodyweight defibrotide or placebo (0.9% sodium chloride) period II: vice versa

16 healthy volunteers will receive 2ng/kg bodyweight LPS plus Defibrotide or Placebo 4 healthy volunteers will receive 0.9% saline (NO LPS) plus Defibrotide or Placebo

Group Type ACTIVE_COMPARATOR

Defibrotide

Intervention Type DRUG

6.25mg/kg bodyweight over 2h infusion

Lipopolysaccharide

Intervention Type DRUG

bolus infusion of 2ng/kg bodyweight lps

Placebo/LPS

2ng/kg lipopolysaccharide period I: 6.25mg/kg bodyweight defibrotide or placebo (0.9% sodium chloride) period II: vice versa

16 healthy volunteers will receive 2ng/kg bodyweight LPS plus Defibrotide or Placebo 4 healthy volunteers will receive 0.9% saline (NO LPS) plus Defibrotide or Placebo

Group Type PLACEBO_COMPARATOR

Placebo (0.9% sodium chloride)

Intervention Type DRUG

(0.9% sodium chloride) infusion over 2h infusion

Lipopolysaccharide

Intervention Type DRUG

bolus infusion of 2ng/kg bodyweight lps

Defibrotide/Placebo

Placebo (0.9% sodium chloride) period I: 6.25mg/kg bodyweight defibrotide or placebo (0.9% sodium chloride) period II: vice versa

16 healthy volunteers will receive 2ng/kg bodyweight LPS plus Defibrotide or Placebo 4 healthy volunteers will receive 0.9% saline (NO LPS) plus Defibrotide or Placebo

Group Type OTHER

Defibrotide

Intervention Type DRUG

6.25mg/kg bodyweight over 2h infusion

Placebo (0.9% sodium chloride bolus)

Intervention Type DRUG

(0.9% sodium chloride) bolus infusion

Placebo/Placebo

Placebo (0.9% sodium chloride) period I: 6.25mg/kg bodyweight defibrotide or placebo (0.9% sodium chloride) period II: vice versa

16 healthy volunteers will receive 2ng/kg bodyweight LPS plus Defibrotide or Placebo 4 healthy volunteers will receive 0.9% saline (NO LPS) plus Defibrotide or Placebo

Group Type OTHER

Placebo (0.9% sodium chloride)

Intervention Type DRUG

(0.9% sodium chloride) infusion over 2h infusion

Placebo (0.9% sodium chloride bolus)

Intervention Type DRUG

(0.9% sodium chloride) bolus infusion

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Defibrotide

6.25mg/kg bodyweight over 2h infusion

Intervention Type DRUG

Placebo (0.9% sodium chloride)

(0.9% sodium chloride) infusion over 2h infusion

Intervention Type DRUG

Lipopolysaccharide

bolus infusion of 2ng/kg bodyweight lps

Intervention Type DRUG

Placebo (0.9% sodium chloride bolus)

(0.9% sodium chloride) bolus infusion

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Bernd Jilma

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Bernd Jilma

Ao.Univ.Prof.Dr.med

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Bernd Jilma, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, , Austria

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Austria

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

LPS_DF Version 1.4

Identifier Type: -

Identifier Source: org_study_id