Ticagrelor in Human Endotoxemia Response to Human Endotoxemia
Status:
Completed
Trial end date:
2015-12-01
Target enrollment:
Participant gender:
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:
Endpoints: area under the curve of the proinflammatory cytokines TNF-alpha, IL6, IL-10, IL1ra
IL-8, IL-1β, MCP-1 MIP-1a, MIP-1b en IFN; peak concentrations of the various cytokines;
plasma concentration of HMGP1; platelet-monocyte complex formation and markers of platelet
function; plasma concentration of adenosine.