NCT02612480

Ticagrelor in Human Endotoxemia Response to Human Endotoxemia

The Effect of Ticagrelor on the Inflammatory Response to Human Endotoxemia

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: Male
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

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.

Conditions

• Endotoxemia

Interventions

Type	Name	Description
DRUG	ticagrelor	7 day treatment of ticagrelor 2dd90mg after a loading dose of 180mg
DRUG	Clopidogrel	7 day treatment of clopidogrel 1d75mg after a loading dose of 300mg
DRUG	Acetylsalicylic acid lysinate	7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg
DRUG	Placebo	7 day treatment with placebo

Timeline

• Start date: 2015-10-01
• Primary completion: 2015-12-01
• Completion: 2015-12-01
• First posted: 2015-11-23
• Last updated: 2015-12-15

Locations

1 site across 1 country: Netherlands