Ticagrelor in Human Endotoxemia Response to Human Endotoxemia

NCT ID: NCT02612480

Last Updated: 2015-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2015-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Endotoxemia

Keywords

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endotoxin LPS ticagrelor clopidogrel acetylsalicyclic acid placebo

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

ticagrelor

Intervention Type DRUG

7 day treatment of ticagrelor 2dd90mg after a loading dose of 180mg

Acetylsalicylic acid lysinate

Intervention Type DRUG

7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg

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

Group Type ACTIVE_COMPARATOR

Clopidogrel

Intervention Type DRUG

7 day treatment of clopidogrel 1d75mg after a loading dose of 300mg

Acetylsalicylic acid lysinate

Intervention Type DRUG

7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg

Placebo and acetylsalicylic acid

7 day treatment with placebo and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg

Group Type PLACEBO_COMPARATOR

Acetylsalicylic acid lysinate

Intervention Type DRUG

7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg

Placebo

Intervention Type DRUG

7 day treatment with placebo

Placebo

7 day treatment with 2 placebos

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

7 day treatment with placebo

Interventions

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ticagrelor

7 day treatment of ticagrelor 2dd90mg after a loading dose of 180mg

Intervention Type DRUG

Clopidogrel

7 day treatment of clopidogrel 1d75mg after a loading dose of 300mg

Intervention Type DRUG

Acetylsalicylic acid lysinate

7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg

Intervention Type DRUG

Placebo

7 day treatment with placebo

Intervention Type DRUG

Other Intervention Names

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brillique Plavix Aspirin

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Peter Pickkers

Prof. Dr. Peter Pickkers

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Peter Pickkers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Niels Riksen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Intensive Care Medicine, Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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2014-005537-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL51923.091.14

Identifier Type: OTHER

Identifier Source: secondary_id

tica-lps

Identifier Type: -

Identifier Source: org_study_id