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Trial record 49 of 507 for:    ASPIRIN AND P2

Ticagrelor in Human Endotoxemia Response to Human Endotoxemia

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ClinicalTrials.gov Identifier: NCT02612480
Recruitment Status : Completed
First Posted : November 23, 2015
Last Update Posted : December 15, 2015
Sponsor:
Information provided by (Responsible Party):
Peter Pickkers, Radboud University

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:

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.


Condition or disease Intervention/treatment Phase
Endotoxemia Drug: ticagrelor Drug: Clopidogrel Drug: Acetylsalicylic acid lysinate Drug: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Ticagrelor on the Inflammatory Response to Human Endotoxemia
Study Start Date : October 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ticagrelor and acetylsalicylic acid
7 day treatment with ticagrelor 2x90mg after a loading dose of 180 mg and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg.
Drug: ticagrelor
7 day treatment of ticagrelor 2dd90mg after a loading dose of 180mg
Other Name: brillique

Drug: Acetylsalicylic acid lysinate
7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg
Other Name: Aspirin

Active Comparator: Clopidogrel and acetylsalicylic acid
7 day treatment with clopidogrel x75 mg after a loading dose of 300 mg and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg
Drug: Clopidogrel
7 day treatment of clopidogrel 1d75mg after a loading dose of 300mg
Other Name: Plavix

Drug: Acetylsalicylic acid lysinate
7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg
Other Name: Aspirin

Placebo Comparator: Placebo and acetylsalicylic acid
7 day treatment with placebo and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg
Drug: Acetylsalicylic acid lysinate
7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg
Other Name: Aspirin

Drug: Placebo
7 day treatment with placebo

Placebo Comparator: Placebo
7 day treatment with 2 placebos
Drug: Placebo
7 day treatment with placebo




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


Secondary Outcome Measures :
  1. concentration plasma IL-6 (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  2. concentration plasma IL-8 (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  3. concentration plasma IL-10 (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  4. concentration plasma IL-1RA (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  5. concentration plasma IL-1beta (pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  6. concentration plasma MCP-1(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  7. concentration plasma MIP-1a(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  8. concentration plasma MIP-1b(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
  9. concentration plasma IFNgamma(pg/ml) [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with Luminex assay

  10. plasma adenosine [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
  11. platelet monocyte complexes [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    flowcytometric determination of monocytic load with platelets

  12. platelet neutrophil complexes [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    flowcytometric determination of neutrophil load with platelets

  13. 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)

  14. 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

  15. monocytic HLA-DR expression [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    as measured by flow cytometry

  16. CD14/16 ratio [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with flow cytometry

  17. platelet von Willebrandfactor expression [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    measured with flow cytometry

  18. VASP-P [ Time Frame: difference between measurement prior to start of study drug after challenge with endotoxin at day 7 of medication ]
    ELISA

  19. symptoms during endotoxin day [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    6 point likert scale

  20. blood pressure [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    mmHg

  21. temperature [ Time Frame: measured after challenge with endotoxin at day 7 of medication ]
    tympanic temperature



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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age ≥ 18 and ≤ 35 years
  • Male
  • No known current medical/psychiatric diseases

Exclusion Criteria:

  • History, signs or symptoms of any cardiovascular disease
  • History of chronic obstructive pulmonary disease (COPD) or asthma
  • History of hemorrhagic diathesis, or any other disorder associated with increased risk of bleeding
  • Previous spontaneous vagal collapse
  • Use of any medication
  • Smoking
  • Liver enzyme abnormalities (defined as ALAT and/or ASAT > twice upper limit of normality)
  • Thrombocytopenia (<150*109

    /ml) or anemia (haemoglobin < 8.0 mmol/L)

  • Any obvious disease associated with immune deficiency
  • Febrile illness in the week before the LPS challenge
  • Hypersensitivity to ticagrelor or any excipients
  • Active pathological bleeding
  • History of intracranial haemorrhage
  • History of dyspepsia
  • quantitative bleeding assessment tool (BAT) score >3 (see Appendix 1)
  • Participation in another drug trial or donation of blood 3 months prior, until 3 months after the planned LPS challenge
  • Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block, third degree atrioventricular block or a complex bundle branch block
  • Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
  • Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
  • Renal impairment (defined as MDRD < 60 ml/min)

Information from the National Library of Medicine

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): NCT02612480


Locations
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Netherlands
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
Investigators
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Principal Investigator: Peter Pickkers, MD, PhD Radboud University
Principal Investigator: Niels Riksen, MD, PhD Radboud University

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Responsible Party: Peter Pickkers, Prof. Dr. Peter Pickkers, Radboud University
ClinicalTrials.gov Identifier: NCT02612480     History of Changes
Other Study ID Numbers: tica-lps
2014-005537-30 ( EudraCT Number )
NL51923.091.14 ( Other Identifier: CCMO )
First Posted: November 23, 2015    Key Record Dates
Last Update Posted: December 15, 2015
Last Verified: December 2015
Keywords provided by Peter Pickkers, Radboud University:
endotoxin
LPS
ticagrelor
clopidogrel
acetylsalicyclic acid
placebo
Additional relevant MeSH terms:
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Aspirin
Acetylsalicylic acid lysinate
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Endotoxemia
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Cyclooxygenase Inhibitors