The Antiplatelet and Immune Response Trial

NCT ID: NCT01846559

Last Updated: 2021-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2014-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Clopidogrel & Endotoxin

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

Group Type: EXPERIMENTAL

Endotoxin

Intervention Type: BIOLOGICAL

E.coli Endotoxin Day 7 - 2 ng/kg

Clopidogrel

Intervention Type: DRUG

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

No antiplatelet medication & Endotoxin

No antiplatelet medication

E.coli Endotoxin Day 7 - 2 ng/kg

Group Type: PLACEBO_COMPARATOR

Endotoxin

Intervention Type: BIOLOGICAL

E.coli Endotoxin Day 7 - 2 ng/kg

Ticagrelor & Endotoxin

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

Group Type: EXPERIMENTAL

Endotoxin

Intervention Type: BIOLOGICAL

E.coli Endotoxin Day 7 - 2 ng/kg

Ticagrelor

Intervention Type: DRUG

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

Interventions

Endotoxin

E.coli Endotoxin Day 7 - 2 ng/kg

Intervention Type: BIOLOGICAL

Clopidogrel

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

Intervention Type: DRUG

Ticagrelor

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

Intervention Type: DRUG

Other Intervention Names

E.coli Endotoxin; Brilique

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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 any prescribed systemic or topical medication within two weeks prior to the start of dosing. Limited use of paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) prior to the initiation of the study will not necessarily require exclusion unless there is an ongoing requirement for these medications.
• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Sheffield

OTHER

Sponsor Role: collaborator

Sheffield Teaching Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Storey, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Sheffield / Sheffield Teaching Hospitals NHS Foundation Trust

Locations

Sheffield Clinical Research Facility

Sheffield, South Yorkshire, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26515417 (View on PubMed)

Other Identifiers

STH17062

Identifier Type: -

Identifier Source: org_study_id