Vorapaxar in LPS induced acute inflammatory states in healthy volunteers

Phase 1

Conditions: PS induced acute inflammatory state in healthy volunteers
Therapeutic area: Not possible to specify

Registration Number: EUCTR2016-000309-34-AT

Lead Sponsor: Medical University of Vienna

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

•=18 years of age
•=60 kg bodyweight
•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
•Willingness to comply with the trial’s safety demands (to refrain from excessive sporting activities two weeks after Vorapaxar intake, i.e. full contact sports, climbing, mountain biking etc.)
•Ability to understand the purpose and nature of the study, as well as the associated risks
•No planned surgeries or other medical interventions in the planned study period

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Intake of any drugs that may interfere with the trial’s endpoints or drugs (i.e. platelet inhibitors, anticoagulants, CYP3A4 inhibitors, NSAIDs, SSRI, SNRI)
•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
•History of stroke, transient ischemic attacks or intracerebral hemorrhage
•Known coagulation or platelet disorders
•Participation in an LPS trial within 6 weeks of the first study day
•Severe liver or kidney dysfunction

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate whether vorapaxar reduces LPS induced coagulation activation assessed by prothrombin fragments F1+2;Secondary Objective: to investigate whether vorapaxar reduces LPS induced:<br>- coagulation activation and fibrinolysis (TAT, DDimer, PAP, etc.)<br>- platelet activation and aggregation (PF4, Whole blood aggregometry, Verify now, etc.)<br>- endothelial activation (vWF activity, endothelial glycocalyx thickness etc.)<br>- cell counts and subsets of monocytes<br>effects of endotoxemia on:<br>platelet proteasome, neutrophil patterns (facs), platelet activation and LPS washout effects<br>;Primary end point(s): prothrombin fragments F1+2;Timepoint(s) of evaluation of this end point: repeated measures between two study periods (placebo vs. vorapaxar, crossover study)<br>two to four hours after lps bolus usually highest values of prothrombin fragments F1+2 are measured. Thus, main effects will be measured at that time point.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -coagulation activation and fibrinolysis (TAT, PAP, tpa, thrombelastometry etc.)<br>- platelet activation and aggregation (PF4, Whole blood aggregometry, Verify now, proteasome etc.)<br>- inflammation and endothelial activation (endothelial glycocalyx, vWF, etc., TSP-1)<br>- cell counts and monocyte/neutrophil subsets;Timepoint(s) of evaluation of this end point: -24h as baseline<br>0h before LPS, but 24h after vorapaxar<br>1h<br>1,5h<br>2h<br>4h<br>6h<br>8h<br>24h after LPS infusion