The Role of the P2Y12 Receptor in Tissue Factor Induced Coagulation
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|ClinicalTrials.gov Identifier: NCT01099566|
Recruitment Status : Completed
First Posted : April 7, 2010
Last Update Posted : July 11, 2011
Severe sepsis still carries a high mortality rate despite advantages in intensive care medicine and antimicrobial therapy. The inflammatory and procoagulant host response to infection are intricately linked and interactions between platelets, leukocytes and the endothelium play a central role in the pathogenesis of septic shock and disseminated intravascular coagulation (DIC). Interestingly, one key player cell in coagulation, i.e. the platelet, has been somewhat neglected as to its position in the pathogenesis of coagulation abnormalities in sepsis. However, thienopyridines, irreversible platelet P2Y12 ADP-receptor antagonists, e.g. prasugrel, could potentially provide beneficial anticoagulatory and antiinflammatory effects: P2Y12 ADP-receptor antagonists reduce TF-induced coagulation activation in various ex vivo and in vitro models. Moreover, various lines of evidence indicate that thienopyridines may block platelet leukocyte interactions and thereby reduce the propagation of the coagulation and inflammation process.
LPS-infusion in healthy volunteers provides a standardized model to safely study non overt DIC and to document possible effects of therapeutic and prophylactic interventions.
The investigators hypothesize that thienopyridines, irreversible platelet P2Y12 ADP-receptor antagonists, may blunt TF-triggered coagulation activation in humans, which will be studied in a TF-dependent coagulation model in humans.
|Condition or disease||Intervention/treatment||Phase|
|Healthy Volunteers Sepsis||Drug: Prasugrel Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Role of the P2Y12 Receptor in Tissue Factor Induced Coagulation|
|Study Start Date :||November 2009|
|Actual Primary Completion Date :||October 2010|
|Actual Study Completion Date :||November 2010|
Prasugrel will be given as loading dose (60mg) on the first trial day two hours prior to endotoxin infusion. Prasugrel is an orally administered prodrug that is converted in the liver by CYP to its active metabolite.
|Placebo Comparator: pills consisting of lactose-starch||
A pharmacist not otherwise involved in the trial will encapsulate pills consisting of lactose-starch. Six pills will be administered as placebo 2 hours before LPS administration on trial day 1.
- prothrombin fragments (F1+2) [ Time Frame: -2 to 24 hours after LPS infusion ]To explore whether P2Y12 ADP-receptor antagonism can block activation of the coagulation cascade induced by endotoxemia, in particular decrease LPS mediated thrombin formation as measured by prothrombin fragment (F1+2).
- platelet-leukocyte co-aggregation [ Time Frame: -2 to 24 hours after LPS infusion ]to explore whether P2Y12 ADP-receptor antagonism decreases platelet -leukocyte co-aggregation
- tissue factor expression [ Time Frame: -2 to 24 hours after LPS infusion ]to investigate the influence of P2Y12 ADP-receptor antagonism on tissue factor expression
- anti-platelet effects of prasugrel [ Time Frame: -2 to 24 hours after LPS infusion ]to explore if low dose endotoxemia interferes with the anti-platelet effects of prasugrel
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01099566
|Medical University of Vienna, Department of Clinical Pharmacology|
|Vienna, Austria, A-1090|
|Principal Investigator:||Bernd Jilma, MD||Medical University of Vienna|