Condition category
Injury, Occupational Diseases, Poisoning
Date applied
06/10/2006
Date assigned
14/03/2007
Last edited
15/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Pascal McKeown

ORCID ID

Contact details

Consultant/Senior Lecture in Cardiology
Royal Hospitals Trust
West Wing
First Floor
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 28 906 32519
p.p.mckeown@qub.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RGHT000270

Study information

Scientific title

The pharmacogenetics of aspirin resistance

Acronym

Study hypothesis

The 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

Approval received from the Office for Research Ethics Committees Northern Ireland (ORECNI) on the 14th June 2006 (reference number: 06/NIR01/44).

Study design

Randomised repeated period crossover trial design

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Condition

Aspirin resistance

Intervention

The 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 type

Drug

Phase

Not Specified

Drug names

Aspirin

Primary outcome measures

1. 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 measures

1. 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 trial start date

01/08/2006

Overall trial end date

30/08/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Healthy individuals aged between 18 to 60 years

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

150 (53 participants actually recruited)

Participant exclusion criteria

Current 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

Recruitment start date

01/08/2006

Recruitment end date

30/08/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Sponsor information

Organisation

Royal Group of Hospitals Trust (UK)

Sponsor details

Royal Research Office
First Floor
Education Centre
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 (0)28 9063 5372
i.young@qub.ac.uk

Sponsor type

Hospital/treatment centre

Website

http://www.royalhospitals.org/

Funders

Funder type

Hospital/treatment centre

Funder name

Royal Hospitals Trust Clinical Fellowship (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Northern Ireland Chest Heart & Stroke Association (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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