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Trial registered on ANZCTR


Registration number
ACTRN12616001508460
Ethics application status
Approved
Date submitted
28/10/2016
Date registered
1/11/2016
Date last updated
10/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of aspirin and ticagrelor on infection-mediated platelet activation in healthy volunteers.
Scientific title
What is the extent to which platelet activation in response to infectious agents is reduced following administration of aspirin and ticagrelor in healthy volunteers?
Secondary ID [1] 290405 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute coronary syndrome 300742 0
Condition category
Condition code
Cardiovascular 300573 300573 0 0
Coronary heart disease
Blood 300593 300593 0 0
Normal development and function of platelets and erythrocytes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Name of intervention: anti-platelet medication.

Arm 1: aspirin alone. Oral administration of 300 mg aspirin (loading dose) on day 1, oral administration of 100 mg aspirin (100 mg once daily, maintenance dose) on days 2 to 7. Total duration is 7 days.

Arm 2: Aspirin and ticagrelor. Oral administration of aspirin, as described in arm 1. Oral administration of 180 mg ticagrelor (loading dose) on day 1, oral administration of 180 mg ticagrelor (90 mg bi-daily, maintenance dose) on days 2 to 7. Total duration is 7 days.

Washout period: 20 days.

Empty drug container to be returned following each anti-platelet drug regimen to ensure adherence to each intervention.

Participants will not be exposed to infectious agents as a part of this trial. Blood will be drawn before and after each anti-platelet drug regimen. Platelets will be isolated from this blood sample and incubated with synthetic infectious agents ex vivo.
Intervention code [1] 296236 0
Treatment: Drugs
Comparator / control treatment
This study involves comparing between 'aspirin alone' and 'aspirin + ticagrelor'.
Control group
Active

Outcomes
Primary outcome [1] 299993 0
Platelet activation in response to infectious agents is the primary outcome of this study.

This is a basic science study and involves in vitro testing of blood samples. The methodology for assessing platelet activation is outlined below.

Platelets will be isolated from whole blood and incubated with 2 TLR agonists (synthetic infectious agents) at various concentrations. These concentrations will produce approximately 50%, 20% and 10% platelet activation at the baseline (before anti-platelet regimen) blood test. Platelet activation following anti-platelet treatment will be assessed against this baseline for each volunteer to determine the extent to which platelet activation is reduced following treatment. In this way, each volunteer acts as their own control for each drug regimen.

Platelet activation will be assessed by flow cytometry. Following incubation with TLR agonists (synthetic infectious agents), platelets will be incubated with anti-CD62p and anti-PAC1 antibodies. This will allow detection of CD62p+ and PAC1+ platelets by flow cytometry, which indicates an activated platelet. Platelet activation will be reported as the percentage of the whole platelet population that is expressing CD62p or PAC1,
Timepoint [1] 299993 0
Baseline (day 1) + immediately following each anti-platelet medication regime (day 8)
Secondary outcome [1] 328767 0
Platelet aggregation in response to arachidonic acid and ADP.

Platelet aggregation will be measured in vitro from blood samples using the Multiplate analyzer. This analyzer uses multiple electrode aggregometry, whereby a blood sample will be incubated with arachidonic acid and ADP in a test cell. Platelets will become activated in response to these agonists and will aggregate on 2 electrodes within the test cell. The extent to which platelet aggregation impedes the electrical current that passes across these 2 electrodes is recorded and reported.

Incubation of whole blood with arachidonic acid will test whether platelets were inhibited in response to aspirin. Incubation with ADP will test whether platelets were inhibited in response to ticagrelor.
Timepoint [1] 328767 0
Baseline (day 1) + immediately following each anti-platelet medication regime (day 8)

Eligibility
Key inclusion criteria
Healthy, aged between 45 and 65
Minimum age
45 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
i) known cardiovascular or inflammatory disease,
ii) platelet function disorder,
iii) a platelet count of less than 100x109/L,
iv) taken any anti-platelet, non-steroidal anti-inflammatory drugs or any cardiovascular or immune-modulating medication within 7 days prior to recruitment,
v) acute illness within 6 weeks prior to recruitment,
vi) pregnancy,
vii) diabetes mellitus,
viii) inability to provide written informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed by using numbered containers which hold the study drugs.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
9/01/2017
Actual
10/03/2017
Date of last participant enrolment
Anticipated
28/02/2017
Actual
14/04/2017
Date of last data collection
Anticipated
31/03/2017
Actual
19/05/2017
Sample size
Target
10
Accrual to date
Final
10
Recruitment outside Australia
Country [1] 8355 0
New Zealand
State/province [1] 8355 0
Wellington

Funding & Sponsors
Funding source category [1] 294814 0
University
Name [1] 294814 0
Victoria University of Wellington
Country [1] 294814 0
New Zealand
Primary sponsor type
Individual
Name
Kathryn Hally
Address
Clinical Research Laboratory,
Level 8, Clinical Services Block,
Wellington Regional Hospital,
Riddiford Street
Newtown,
Wellington 6021.
Country
New Zealand
Secondary sponsor category [1] 293653 0
None
Name [1] 293653 0
N/A
Address [1] 293653 0
N/A
Country [1] 293653 0
Other collaborator category [1] 279281 0
Individual
Name [1] 279281 0
Associate Professor Peter Larsen
Address [1] 279281 0
University of Otago,
Wellington campus,
Mein Street
Newtown,
Wellington 6021.
Country [1] 279281 0
New Zealand
Other collaborator category [2] 279282 0
Individual
Name [2] 279282 0
Doctor Scott Harding
Address [2] 279282 0
Department of Cardiology,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021.
Country [2] 279282 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296203 0
Health and Disability Ethics Committee
Ethics committee address [1] 296203 0
Ministry of Health,
Ethics Department,
Freyberg Building,
Reception – Ground Floor,
20 Aitken Street,
Wellington 6011.
Ethics committee country [1] 296203 0
New Zealand
Date submitted for ethics approval [1] 296203 0
08/11/2016
Approval date [1] 296203 0
07/03/2017
Ethics approval number [1] 296203 0
16/STH/240

Summary
Brief summary
We are inviting healthy individuals to take part in a study that is investigating how platelet activation in response to infection is reduced following administration of anti-platelet therapy. Platelets are blood clotting cells that usually act to repair damage to blood vessels. However, these cells also cause blood clots in the arteries of the heart and this can cause a heart attack. Platelets participate in a heart attack by becoming activated. People with heart attacks are treated with anti-platelet drugs that prevent platelet activation and reduce the risk of having another heart attack. We have previously shown that platelets can become activated in response to infection. However, it is unclear to what extent treatment with anti-platelet medication can inhibit platelet activation in response to infection.

We aim to investigate how platelet activation in response to infection is reduced with anti-platelet medication.

Once recruited, each healthy volunteer will be asked to take 2 courses of anti-platelet medication, each one for 7 days. There will be a 'before' and 'after' blood test for each of these courses (totalling 4 blood tests). Each volunteer will participate in thus study for a total of 5 weeks.

If we determine, from this study, that platelet activation is reduced only slightly by anti-platelet medication, patients that have a heart attack and also experience an infection could have high platelet activation, despite being optimally treated. They may experience a recurrent heart attack as a result. This study will, therefore, determine whether there is a gap in the treatment of this group of patients and whether treatment for these patients needs to be revised.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69982 0
Miss Kathryn Hally
Address 69982 0
Clinical Research Laboratory,
Level 8, Clinical Services Block,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021.
Country 69982 0
New Zealand
Phone 69982 0
+6444636559
Fax 69982 0
Email 69982 0
[email protected]
Contact person for public queries
Name 69983 0
Miss Kathryn Hally
Address 69983 0
Clinical Research Laboratory,
Level 8, Clinical Services Block,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021.
Country 69983 0
New Zealand
Phone 69983 0
+6444636559
Fax 69983 0
Email 69983 0
[email protected]
Contact person for scientific queries
Name 69984 0
Miss Kathryn Hally
Address 69984 0
Clinical Research Laboratory,
Level 8, Clinical Services Block,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021.
Country 69984 0
New Zealand
Phone 69984 0
+6444636559
Fax 69984 0
Email 69984 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe effects of aspirin and ticagrelor on Toll-like receptor (TLR)-mediated platelet activation: results of a randomized, cross-over trial.2019https://dx.doi.org/10.1080/09537104.2018.1479520
N.B. These documents automatically identified may not have been verified by the study sponsor.