Vorapaxar in the Human Endotoxemia Model
Condition: Healthy Volunteers
MeSH terms: Endotoxemia
Intervention: Vorapaxar; Placebo; LPS
Intervention description: 10mg-20mg vorapaxar to achieve >80% thrombin-receptor activated peptide-6 (TRAP) induced platelet inhibition; 2ng/kg Lipopolysaccharide as a bolus infusion
Intervention MeSH terms: Vorapaxar
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Coagulations; Platelets; Inflammation; endotoxemia; vorapaxar

Summary:

      Vorapaxar is a recently approved protease activated receptor - 1 (PAR-1) inhibitor. Platelet
      inhibition may also exert positive results on coagulation activation and may beneficially
      influence the inflammatory response. Since vorapaxar is the first available substance of a
      new class of platelet inhibitors its effects on the human coagulation system and the
      inflammatory response will be assessed in the well-established human endotoxemia model.
    

Eligibility criteria:

        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

        Exclusion Criteria:

          -  Intake of any drugs that may interfere with the trial's endpoints or drugs (i.e.
             platelet inhibitors, anticoagulants, CYP3A4 inhibitors, NSAIDs, selective serotonin
             reuptake inhibitors, selective noradrenaline and serotonin reuptake inhibitors)

               -  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

               -  Pregnancy or breastfeeding