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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02612480
Other study ID # tica-lps
Secondary ID 2014-005537-30NL
Status Completed
Phase N/A
First received November 3, 2015
Last updated December 14, 2015
Start date October 2015
Est. completion date December 2015

Study information

Verified date December 2015
Source Radboud University
Contact n/a
Is FDA regulated No
Health authority Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 40
Est. completion date December 2015
Est. primary completion date December 2015
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 18 Years to 35 Years
Eligibility 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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Basic Science


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Netherlands Intensive Care Medicine, Radboud University Nijmegen Medical Centre Nijmegen Gelderland

Sponsors (1)

Lead Sponsor Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary concentration plasma TNFalpha (pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma IL-6 (pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma IL-8 (pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma IL-10 (pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma IL-1RA (pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma IL-1beta (pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma MCP-1(pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma MIP-1a(pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma MIP-1b(pg/ml) measured after challenge with endotoxin at day 7 of medication No
Secondary concentration plasma IFNgamma(pg/ml) measured with Luminex assay measured after challenge with endotoxin at day 7 of medication No
Secondary plasma adenosine measured after challenge with endotoxin at day 7 of medication No
Secondary platelet monocyte complexes flowcytometric determination of monocytic load with platelets measured after challenge with endotoxin at day 7 of medication No
Secondary platelet neutrophil complexes flowcytometric determination of neutrophil load with platelets measured after challenge with endotoxin at day 7 of medication No
Secondary platelet reactivity ex vivo stimulation of platelets with ADP and collagen, response measured as P-selectin and fibrinogen) measured after challenge with endotoxin at day 7 of medication No
Secondary monocytic tissue factor expression tissue factor expression on monocytes as measured by flow cytometry measured after challenge with endotoxin at day 7 of medication No
Secondary monocytic HLA-DR expression as measured by flow cytometry measured after challenge with endotoxin at day 7 of medication No
Secondary CD14/16 ratio measured with flow cytometry measured after challenge with endotoxin at day 7 of medication No
Secondary platelet von Willebrandfactor expression measured with flow cytometry measured after challenge with endotoxin at day 7 of medication No
Secondary VASP-P ELISA difference between measurement prior to start of study drug after challenge with endotoxin at day 7 of medication No
Secondary symptoms during endotoxin day 6 point likert scale measured after challenge with endotoxin at day 7 of medication No
Secondary blood pressure mmHg measured after challenge with endotoxin at day 7 of medication No
Secondary temperature tympanic temperature measured after challenge with endotoxin at day 7 of medication No
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