Ticagrelor in Human Endotoxemia Response to Human Endotoxemia

NCT02612480 | Completed DMC

• 3 other identifiers: tica-lps2014-005537-30NL51923.091.14
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Endotoxemia

Keywords

endotoxin; LPS; ticagrelor; clopidogrel; acetylsalicyclic acid; placebo

Outcome Measures

Primary Outcomes (1)

• concentration plasma TNFalpha (pg/ml)

  measured with Luminex assay

  measured after challenge with endotoxin at day 7 of medication

Secondary Outcomes (21)

• concentration plasma IL-6 (pg/ml)

  measured after challenge with endotoxin at day 7 of medication

• concentration plasma IL-8 (pg/ml)

  measured after challenge with endotoxin at day 7 of medication

• concentration plasma IL-10 (pg/ml)

  measured after challenge with endotoxin at day 7 of medication

• concentration plasma IL-1RA (pg/ml)

  measured after challenge with endotoxin at day 7 of medication

• concentration plasma IL-1beta (pg/ml)

  measured after challenge with endotoxin at day 7 of medication

Study Arms (4)

Ticagrelor and acetylsalicylic acid

EXPERIMENTAL

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; Drug: Acetylsalicylic acid lysinate

Clopidogrel and acetylsalicylic acid

ACTIVE COMPARATOR

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; Drug: Acetylsalicylic acid lysinate

Placebo and acetylsalicylic acid

PLACEBO COMPARATOR

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

Drug: Acetylsalicylic acid lysinate; Drug: Placebo

Placebo

PLACEBO COMPARATOR

7 day treatment with 2 placebos

Drug: Placebo

Interventions

ticagrelor DRUG

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

Also known as: brillique

Ticagrelor and acetylsalicylic acid

Clopidogrel DRUG

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

Also known as: Plavix

Clopidogrel and acetylsalicylic acid

Acetylsalicylic acid lysinate DRUG

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

Also known as: Aspirin

Clopidogrel and acetylsalicylic acid; Placebo and acetylsalicylic acid; Ticagrelor and acetylsalicylic acid

Placebo DRUG

7 day treatment with placebo

Placebo; Placebo and acetylsalicylic acid

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Intensive Care Medicine, Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500HB, Netherlands

Location

MeSH Terms

Conditions

Endotoxemia

Interventions

Ticagrelor; Clopidogrel; acetylsalicylic acid lysinate; Aspirin

Condition Hierarchy (Ancestors)

Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Niels Riksen, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Peter Pickkers

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 23, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 15, 2015

Record last verified: 2015-12

Locations

NL (1)