The Antiplatelet and Immune Response Trial

NCT01846559 | Completed Phase 4 DMC

• 1 other identifier: STH17062
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Platelets are the main type of blood cell involved in the formation of blood clots that cause heart attacks. The investigators give antiplatelet drugs (aspirin, for example) to reduce the risk of another clot forming in the future and causing another heart attack. Platelets are known to have a role in inflammation and infection as well as clotting. In a recent large clinical trial, known as the PLATO study, it was also shown that patients treated with a new antiplatelet medication (ticagrelor) developed fewer lung infections, as well as fewer heart attacks, compared to the current standard treatment (clopidogrel). The investigators would therefore like to investigate the reasons behind this and look at the effect of these medications on immune response. This may help us develop new drugs that have a better effect on immune response. The investigators are planning a clinical trial that investigates the effect of these medications on the immune response of healthy volunteers aged 18 to 65. Only volunteers with no significant past medical history and not taking any medications will be included. Thirty volunteers will receive either a normal dose of ticagrelor or clopidogrel or no antiplatelet medication for 1 week. They will then attend the Sheffield Clinical Research Facility where their immune response will be stimulated using a safe, well established method. The investigators will do this with an injection of a low dose of endotoxin, which is part of the surface coating of some bacteria and has been used extensively in similar studies, in over a thousand volunteers over the past 20 years to investigate immune response. It is known to cause temporary flu-like symptoms that last approximately 68 hours. The investigators will take measurements of inflammatory markers, white blood cell function and platelet function and compare the effect of ticagrelor and clopidogrel on this immune response.

Conditions

Healthy

Keywords

Immune system processes

Outcome Measures

Primary Outcomes (1)

• Area under the curve of graph of C-reactive protein over time over 24 hours following administration of endotoxin

  24 hours

Study Arms (3)

Clopidogrel & Endotoxin

EXPERIMENTAL

Clopidogrel (tablet) over 8 days Day 1: 300 mg loading dose Day 2-7: 75 mg orally once daily E.coli Endotoxin Day 7 - 2 ng/kg

Biological: Endotoxin; Drug: Clopidogrel

No antiplatelet medication & Endotoxin

PLACEBO COMPARATOR

No antiplatelet medication E.coli Endotoxin Day 7 - 2 ng/kg

Biological: Endotoxin

Ticagrelor & Endotoxin

EXPERIMENTAL

Ticagrelor over 8 days (tablet) Day 1: 180 mg loading dose Day 2-7: 90 mg orally twice daily E.coli Endotoxin Day 7 - 2 ng/kg

Biological: Endotoxin; Drug: Ticagrelor

Interventions

Endotoxin BIOLOGICAL

E.coli Endotoxin Day 7 - 2 ng/kg

Also known as: E.coli Endotoxin

Clopidogrel & Endotoxin; No antiplatelet medication & Endotoxin; Ticagrelor & Endotoxin

Clopidogrel DRUG

Clopidogrel (tablet) over 8 days Day 1: 300 mg loading dose Day 2-7: 75 mg orally once daily

Clopidogrel & Endotoxin

Ticagrelor DRUG

Ticagrelor over 8 days (tablet) Day 1: 180 mg loading dose Day 2-7: 90 mg orally twice daily

Also known as: Brilique

Ticagrelor & Endotoxin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post menopausal)
• Age between 18 and 65 years inclusive
• Non smokers
• Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg
• Subjects are to be in good health as determined by a medical history, physical examination, vital signs and clinical laboratory test results including renal and liver function and full blood count
• Subjects have given their informed consent before any trial-related activity

You may not qualify if:

• In the opinion of the investigator, subjects with, or a history of, cancer, diabetes or clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric, or other major disorders
• Subjects with a history of significant multiple drug allergies or with a known allergy to the study drugs or a medicine chemically related to the trial product
• Subjects who have had a clinically significant illness within 4 weeks of dosing
• Subjects taking regular medicines including NSAIDs, antibiotics, aspirin or anticoagulant therapy
• Any clinically significant abnormal laboratory test results at screening
• Subjects who have a supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg
• Subjects who have a supine heart rate at screening, after resting for 5 minutes, outside the range of 50-100 beats/min
• Subjects who have received an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three months preceding the start of dosing
• Subjects who have donated any blood or plasma in the month preceding the start of dosing
• Subjects who have a history of alcohol or drug abuse
• Subjects with mental incapacity or language barriers which preclude adequate understanding
• Subjects with a contraindication to ticagrelor (as listed in the SmPC - hypersensitivity to the active substance or any of its excipients, active pathological bleeding, history of intracranial hemorrhage, moderate to severe hepatic impairment and co-administration with strong CYP3A4 inhibitors)
• Subjects with a contraindication to clopidogrel (as listed in the SmPC - hypersensitivity to the active substance or any of its excipients, severe hepatic impairment, active pathological bleeding such as peptic ulcer or intracranial haemorrhage)

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator

Study Sites (1)

Sheffield Clinical Research Facility

Sheffield, South Yorkshire, S5 7AU, United Kingdom

Location

Related Publications (1)

• Thomas MR, Outteridge SN, Ajjan RA, Phoenix F, Sangha GK, Faulkner RE, Ecob R, Judge HM, Khan H, West LE, Dockrell DH, Sabroe I, Storey RF. Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model. Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2562-70. doi: 10.1161/ATVBAHA.115.306528. Epub 2015 Oct 29.

  PMID: 26515417 DERIVED

MeSH Terms

Interventions

Endotoxins; Clopidogrel; Ticagrelor

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Robert Storey, Prof

  University of Sheffield / Sheffield Teaching Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 3, 2013
• Study Start: April 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: September 27, 2021

Record last verified: 2021-09

Locations

GB (1)