ISRCTN ISRCTN71079188
DOI https://doi.org/10.1186/ISRCTN71079188
Secondary identifying numbers RGHT000270
Submission date
06/10/2006
Registration date
14/03/2007
Last edited
15/04/2016
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Injury, Occupational Diseases, Poisoning
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Pascal McKeown
Scientific

Consultant/Senior Lecture in Cardiology
Royal Hospitals Trust
West Wing, First Floor
Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Phone +44 28 906 32519
Email p.p.mckeown@qub.ac.uk

Study information

Study designRandomised repeated period crossover trial design
Primary study designInterventional
Secondary study designRandomised cross over trial
Study setting(s)Hospital
Study typeOther
Scientific titleThe pharmacogenetics of aspirin resistance
Study objectivesThe Antiplatelet Trialists' Collaboration meta-analyses (1994) documented a 25% reduction of death, myocardial infarction, and stroke in high-risk patients treated with aspirin. However, some patients continue to experience clinical events despite aspirin therapy, indicating that the anti-platelet effect of aspirin may not be uniform in all patients. Clinical aspirin resistance refers to those patients who have recurrent thrombotic events despite compliance with therapy. Biochemical aspirin refers to inadequate platelet inhibition on formal testing.

The aims of this proposed study are to use a repeated period crossover trial design in order to assess the reproducibility of aspirin resistance in healthy control individuals, using standard optical platelet aggregometry. Additional measures of platelet function will also be assessed using the Platelet Function Analyser (PFA-100) system, and levels of serum thromboxane B2 and urinary 11-dehydro thromboxane B2.

Furthermore, the contribution of genetic polymorphisms in candidate genes to the phenomenon of aspirin resistance will be characterised. Polymorphisms of several contributing genes including the Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), GlycoProtein IIIa (GPIIIA), and adenosine 5-diphosphate receptor genes will be investigated using standard molecular approaches.

01/10/2012: Please note that the anticipated end date of this trial was updated from 01/08/2009 to 30/08/2012
Ethics approval(s)Approval received from the Office for Research Ethics Committees Northern Ireland (ORECNI) on the 14th June 2006 (reference number: 06/NIR01/44).
Health condition(s) or problem(s) studiedAspirin resistance
InterventionThe study is a repeated crossover trial design of two treatments and four periods. The aspirin dose will be either 75 mg or 300 mg but will be fixed within individual patients. A subject will be randomised to one of four treatment sequences: ABBA, BAAB, ABAB or BABA, where A is active drug and B is placebo.

Each individual study period will last for three weeks, therefore the total period of study for each patient will be 12 weeks. This type of design allows the study of treatment, subject, period and carry-over effects, and their interactions, specifically the subject-by-treatment interaction.

The individuals will be seen at baseline and once informed consent has been obtained, baseline tests for platelet function tests (optical aggregometry, PFA-100) and serum/urine thromboxane levels will be taken, as will whole blood for later analysis of genetic polymorphisms. Further samples for platelet function testing will be taken at the end of each crossover period.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Aspirin
Primary outcome measure1. Assess the reproducibility of aspirin resistance in healthy control individuals, as defined by standard optical platelet aggregometry
2. Characterise the contribution of genetic polymorphisms in candidate genes, specifically the cyclooxygenase and adenosine 5-diphosphate receptor genes, to the phenomenon of aspirin resistance
Secondary outcome measures1. The assessment of the reproducibility of aspirin response as defined by other platelet function tests (PFA-100 system, thromboxane levels)
2. The contribution of other genetic polymorphisms to the phenomenon of aspirin resistance
3. The correlation between the various platelet function tests used in this study
Overall study start date01/08/2006
Completion date30/08/2012

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit60 Years
SexNot Specified
Target number of participants150 (53 participants actually recruited)
Key inclusion criteriaHealthy individuals aged between 18 to 60 years
Key exclusion criteriaCurrent exclusion criteria as of 01/10/2012
1. Use of other anti-platelet drugs (thienopyridines, GPIIb/IIIa antagonists, dipyridamole) because these drugs would interfere with platelet function assays
2. Use of other non-steroidal anti-inflammatory drugs, because of the pharmacodynamic interactions
3. History of dyspepsia or peptic ulceration requiring treatment with proton pump inhibitors/H2 antagonists, in view of the increased risk of gastrointestinal haemorrhage
4. History of systemic inflammatory diseases, in view of the need for these patients to take anti-inflammatory drugs
5. History of asthma
6. Use of other aspirin-containing medications (including herbal preparations)
7. Family or personal history of bleeding disorders
8. Use of oral anticoagulants
9. Platelet count outside the normal range (150,000 to 450,000/ml)
10. Significant anaemia (Haemoglobin [Hb] less than 10 g/dl)
11. Recent major surgery
12. Known significant malignant disease
13. known aspirin allergy
14.1 Pregnancy
14.2 Women of childbearing potential except in the following circumstances for the duration of the trial: 'monogamous relationship and partner sterilised' or 'for personal reasons not sexually active' or 'use of double barrier methods of contraception'
15. History of lactose intolerance, as lactose if the primary substance contained in the placebo
16. History of gout, as aspirin can precipitate gout
17. History of severe renal or hepatic dysfunction
18. Planned surgery during participation in trial
19. Excessive alcohol ingestion (more than 40 units per week)
20. Inability to provide informed consent

Previous exclusion criteria until 01/10/2012:
14. Pregnancy/women of childbearing potential
Date of first enrolment01/08/2006
Date of final enrolment30/08/2012

Locations

Countries of recruitment

  • Northern Ireland
  • United Kingdom

Study participating centre

Consultant/Senior Lecture in Cardiology
Belfast
BT12 6BA
United Kingdom

Sponsor information

Royal Group of Hospitals Trust (UK)
Hospital/treatment centre

Royal Research Office
First Floor
Education Centre
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom

Phone +44 (0)28 9063 5372
Email i.young@qub.ac.uk
Website http://www.royalhospitals.org/
ROR logo "ROR" https://ror.org/03rq50d77

Funders

Funder type

Hospital/treatment centre

Royal Hospitals Trust Clinical Fellowship (UK)

No information available

Northern Ireland Chest Heart & Stroke Association (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Editorial Notes

15/04/2016: No publications found, verifying study status with principal investigator.