HealthyPhase 4NCT01846559
The Antiplatelet and Immune Response Trial
A Phase 4 study testing Endotoxin, Clopidogrel and Ticagrelor in people with Healthy, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Endotoxin, Clopidogrel and Ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2013to Jan 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sheffield Clinical Research Facility
Sheffield, South Yorkshire, S5 7AU
About this study
Official title: 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.
Read more
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
- Being tested
- Endotoxin, Clopidogrel, Ticagrelor
- Keywords
- Immune system processes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndotoxinBiological
Also called E.coli Endotoxin
E.coli Endotoxin Day 7 - 2 ng/kg
ClopidogrelDrug
Clopidogrel (tablet) over 8 days Day 1: 300 mg loading dose Day 2-7: 75 mg orally once daily
TicagrelorDrug
Also called Brilique
Ticagrelor over 8 days (tablet) Day 1: 180 mg loading dose Day 2-7: 90 mg orally twice daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Endotoxin; Drug: Clopidogrel |
| No antiplatelet medication & Endotoxin | Placebo comparator | No antiplatelet medication
E.coli Endotoxin Day 7 - 2 ng/kg Receives: 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 Receives: Biological: Endotoxin; Drug: Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve of graph of C-reactive protein over time over 24 hours following administration of endotoxin
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startApr 2013
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sheffield
- Responsible party
- Sponsor
- Investigators
- Robert Storey, Prof, Principal investigator, University of Sheffield / Sheffield Teaching Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01846559
- Sponsor's protocol ID
- STH17062
- Status last verified
- Sep 2021
- First submitted
- 1 May 2013
- Last updated
- 27 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26515417
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effect of Ticagrelor and Clopidogrel on the Immune Response of Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01846559
- Acronym / sponsor ID
- STH17062
- Conditions
- Healthy
- Keywords
- Immune system processes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Sheffield
- Study start
- Apr 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel & Endotoxin | Experimental | Biological: Endotoxin, Drug: ClopidogrelClopidogrel (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 |
| No antiplatelet medication & Endotoxin | Placebo comparator | Biological: EndotoxinNo antiplatelet medication E.coli Endotoxin Day 7 - 2 ng/kg |
| Ticagrelor & Endotoxin | Experimental | Biological: Endotoxin, Drug: TicagrelorTicagrelor 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EndotoxinAlso: E.coli EndotoxinE.coli Endotoxin Day 7 - 2 ng/kg | Biological | Clopidogrel & Endotoxin, No antiplatelet medication & Endotoxin, Ticagrelor & Endotoxin |
| ClopidogrelClopidogrel (tablet) over 8 days Day 1: 300 mg loading dose Day 2-7: 75 mg orally once daily | Drug | Clopidogrel & Endotoxin |
| TicagrelorAlso: BriliqueTicagrelor over 8 days (tablet) Day 1: 180 mg loading dose Day 2-7: 90 mg orally twice daily | Drug | Ticagrelor & Endotoxin |
Primary outcome
Area under the curve of graph of C-reactive protein over time over 24 hours following administration of endotoxin
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2021.
- Derived from this study: PubMed 26515417Thomas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Storey, Prof principal investigator
University of Sheffield / Sheffield Teaching Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Endotoxin, Clopidogrel and Ticagrelor in people with Healthy, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the curve of graph of C-reactive protein over time over 24 hours following administration of endotoxin (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01846559, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2021.