The Antiplatelet and Immune Response Trial

September 21, 2021 updated by: Sheffield Teaching Hospitals NHS Foundation Trust

Study of the Effect of Ticagrelor and Clopidogrel on the Immune Response of Healthy Volunteers

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S5 7AU
        • Sheffield Clinical Research Facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Biological: Endotoxin
E.coli Endotoxin Day 7 - 2 ng/kg
Other Names:
  • E.coli Endotoxin
Drug: Clopidogrel
Clopidogrel (tablet) over 8 days Day 1: 300 mg loading dose Day 2-7: 75 mg orally once daily
PLACEBO_COMPARATOR: No antiplatelet medication & Endotoxin

No antiplatelet medication

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area under the curve of graph of C-reactive protein over time over 24 hours following administration of endotoxin
Time Frame: 24 hours
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Collaborators

University of Sheffield

Investigators

  • Principal Investigator: Robert Storey, Prof, University of Sheffield / Sheffield Teaching Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (ACTUAL)

January 1, 2014

Study Completion (ACTUAL)

January 1, 2014

Study Registration Dates

First Submitted

May 1, 2013

First Submitted That Met QC Criteria

May 2, 2013

First Posted (ESTIMATE)

May 3, 2013

Study Record Updates

Last Update Posted (ACTUAL)

September 27, 2021

Last Update Submitted That Met QC Criteria

September 21, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH17062

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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