Clinical Trial: Ticagrelor in Human Endotoxemia Response to Human Endotoxemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Effect of Ticagrelor on the Inflammatory Response to Human Endotoxemia

Brief Summary:

Rationale:

In patients suffering a myocardial infarction the P2Y12 receptor antagonists prasugrel and ticagrelor improve outcome and prognosis compared to clopidogrel. Moreover, ticagrelor lowers mortality from pulmonary infections and sepsis, which cannot solely be explained by its platelet-inhibiting effect. An effect on the inflammatory response in the setting of acute myocardial might underlie this phenomenon and if substantiated support a novel beneficial mechanism of the new the P2Y12 receptor antagonists.

Objective:

To study whether ticagrelor, added to acetylsalicylic acid, modulates the inflammatory response to the administration of lipopolysaccharide (LPS) in humans in vivo, and to compare this effect with the P2Y12 antagonist clopidogrel.

Study design:

Prospective randomized placebo-controlled trial, according to a PROBE design (prospective randomized open blinded-endpoint study).

Study population:

Forty healthy male volunteers aged ≥ 18 and ≤ 35 years. Intervention (if applicable): Participants will be randomized to receive either placebo (twice daily), acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) + placebo (once daily), acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) + ticagrelor (90 mg twice daily, after a loading dose of 180 mg) or acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg)+ clopidogrel (75 mg once daily, after a loading dose of 300mg).

Main study parameters/endpoints:

Endpo

Detailed Summary:
Sponsor: Radboud University

Current Primary Outcome: concentration plasma TNFalpha (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]

measured with Luminex assay


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • concentration plasma IL-6 (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma IL-8 (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma IL-10 (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma IL-1RA (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma IL-1beta (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma MCP-1(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma MIP-1a(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • concentration plasma MIP-1b(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
  • concentration plasma IFNgamma(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay
  • plasma adenosine [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
  • platelet monocyte complexes [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    flowcytometric determination of monocytic load with platelets
  • platelet neutrophil complexes [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    flowcytometric determination of neutrophil load with platelets
  • platelet reactivity [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    ex vivo stimulation of platelets with ADP and collagen, response measured as P-selectin and fibrinogen)
  • monocytic tissue factor expression [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    tissue factor expression on monocytes as measured by flow cytometry
  • monocytic HLA-DR expression [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    as measured by flow cytometry
  • CD14/16 ratio [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with flow cytometry
  • platelet von Willebrandfactor expression [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with flow cytometry
  • VASP-P [ Time Frame: difference between measurement prior to start of study drug after challenge with endotoxin at day 7 of medication ]
    ELISA
  • symptoms during endotoxin day [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    6 point likert scale
  • blood pressure [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    mmHg
  • temperature [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    tympanic temperature


Original Secondary Outcome: Same as current

Information By: Radboud University

Dates:
Date Received: November 3, 2015
Date Started: October 2015
Date Completion:
Last Updated: December 14, 2015
Last Verified: December 2015