Ischemic StrokeNCT05763862
Genotype Guided Antiplatelet Therapy In Ischemic Stroke
A study testing Genetic testing in people with Ischemic Stroke and Transient Ischemic Attack, run by National Neuroscience Institute at 1 site in Singapore.
Trial summary
A fifth of ischemic stroke or transient ischemic attack (TIA) patients will have recurrent events within the first 3 months [Refs 1-3] despite aggressive medical therapy with antiplatelets and risk factor control. Read more about this study
- Who is it for?
- Ages 21 to 100 years
- Conditions the study is for
- Ischemic Stroke, Transient Ischemic Attack
- What is being tested?
- Genetic testing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 1 siteSingapore
- Study dates
- 24 Apr 2023to Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 21 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with acute ischemic stroke or transient ischemic attack.
- Age 21 years to 100 years.
- Can be randomised within 7 days of onset of index event [Refer to footnote 1].
- Clopidogrel naive immediately prior to index event [Refer to footnote 2].
- Footnote 1: Date of index event to be taken as Day 1. This means that randomisation must be done by Day 7. For unknown onset or wake-up stroke where the last seen well and symptoms discovery are on different days, Day 1 is taken to be the date of symptoms discovery. Footnote 2: Patients who were on short-term antiplatelets which included clopidogrel but are no longer on clopidogrel prior to stroke would fulfil for this inclusion criteria. In this context, short-term antiplatelets are defined as 21 days for minor stroke TIA and 3 months for large vessel disease.
Who cannot join
- Known diagnosis of dementia [Refer to footnote 3].
- Known diagnosis of a life limiting illness with life expectancy of less than 1 year.
- Known cardioembolism or prothrombotic state necessitating the use of anticoagulation, or having a contraindication to clopidogrel.
- Footnote 3: "Known diagnosis of dementia" will be defined as clinical diagnosis of dementia prior to the index stroke event as indicated in the patient's medical records.
Trial locations and contacts
1 site in 1 country.
About this study
A fifth of ischemic stroke or transient ischemic attack (TIA) patients will have recurrent events within the first 3 months [Refs 1-3] despite aggressive medical therapy with antiplatelets and risk factor control.
Clopidogrel is one of the mainstays of antiplatelet secondary prevention therapy in patients with ischemic stroke. CYP2C19 loss of function (LOF) mutations impair the effectiveness of clopidogrel [Ref 4]. The prevalence of LOF mutations is approximately 60% in the local population [Ref 5], rendering the effectiveness of empiric clopidogrel treatment doubtful. For patients who have LOF mutations, other treatment options for secondary prevention of ischemic stroke need to be tested. This study aims to determine the feasibility and clinical impact of genetic testing guided antiplatelet therapy in ischemic stroke patients on the prevention of major adverse cardiovascular or cerebrovascular events.
Clopidogrel naive ischemic stroke or TIA patients aged 21 years and above will be randomised to genetic testing guided antiplatelet therapy or standard medical therapy within 7 days of their index event. Patients allocated to testing group will have blood sample drawn for diagnosis of CYP2C19 LOF mutations. Patients who test positive for an LOF mutation (intermediate and poor metabolisers) will be offered alternative antiplatelet therapy in the form of aspirn (for those who need monotherapy) or aspirin plus ticagrelor or dipyridamole (for those who need dual antiplatelet therapy) to be decided by the managing physician. Patients who test negative for LOF mutation will continue on clopidogrel. Platelet reactivity index (enables the identification of patients with an inadequate response to antiplatelet agents) will be measured at baseline.
Read the detailed description
This is a multicentre, prospective, randomised, open blinded endpoint trial.
The study will include three visits: Baseline (within 1 week of index event), 3 months, and 12 months. Randomisation will be performed for patients with unknown CYP2C19 status while no randomisation will be done for patients with known CYP2C19 status at the time of recruitment. Baseline visit will need to be in-person, whle the 3-month and 12-month follow-ups can either be inperson or via telephone. Data on antiplatelet regimen, MACCE outcomes, and GUSTO outcomes will be collected at the follow-up visits. Blood tests will be performed on the genetic testing guided antiplatelet therapy arm and standard medical therapy arm at baseline to determine the platelet reactivity index (PRI).
Patients with unknown CYP2C19 status will be randomised to genetic testing versus standard medical therapy in a 1:1 ratio, via a block randomisation process. The block randomisation sequence will be generated by a web-based randomisation service in blocks of four for each recruitment site. Blinding is not applicable for the treatment assigned.
Patients randomised to testing will have blood drawn for testing of the CYP2C19 LOF mutations. Physicians of patients who test positive for an LOF mutation (intermediate and poor metabolizers) will be notified of the mutation with recommendations of possible alternative antiplatelet regimens suggested. Aspirin will be the recommended monotherapy, and aspirin in combination with ticagrelor or dipyridamole will be the recommended dual antiplatelet regimen. The decision of alternative medications used in patients with LOF mutations will be left to the discretion of the primary physician. Patients in the standard medical therapy group, and patients in the genotype guided antiplatelet therapy group who do not have LOF mutations (normal metabolisers) will be left to continue the original intended antiplatelet regimen - this may be clopidogrel monotherapy, or in combination with aspirin. Patients who experience recurrent events during follow-up, or who have drug intolerance can be changed from the antiplatelet regimen as per primary physician's discretion. Information on all medications, including antiplatelet regimen at discharge and at subsequent reviews will be collected.
There will be no randomisation for patients with known CYP2C19 status prior to recruitment. Patients with known CYP2C19 status will be recruited as a comparison arm for outcomes measurements.
CYP2C19 genotyping will be performed by the Singapore General Hospital's clinical laboratory services. Turnaround time for CYP2C19 is approximately 7 days. Patient will be notified of CYP2C10 LOF mutation result.
Demographic characteristics that will be ascertained includes age, sex, ethnicity, education level, date of study randomisation. Past medical history will be recorded: hypertension, diabetes, hyperlipidemia, ischemic heart disease, atrial fibrillation, smoking, peripheral vascular disease, previous ischemic stroke/transient ischemic attack, intracranial bleeding, clinically significant bleeding, smoking and alcohol. Information pertaining to hospital admission, stroke characteristics, medications that the patients are on, particularly antiplatelet, anticoagulation, proton pump inhibitor, histamine H2 receptor antagonists, and cardiovascular medication prior to the admission and at discharge will be assessed. Use of single versus dual antiplatelet therapy, and duration of dual antiplatelet therapy will be considered confounders.
For subjects randomised to the standard medical therapy arm, genetic testing for CYP2C19 LOF mutations may be performed for clinical purpose after randomisation and before the end of subject's participation in the study, which could result in treatment changes. Such cases will not be considered as a protocol violation. These subjects will continue with treatment as per advised by the primary physician and may continue study follow ups till the end of the study.
If subjects are identified after randomisation to have cardioembolism or prothrombotic state necessitating the use of anticoagulation, the treating physician should manage as per standard medical care. These will not be considered as protocol violation as the diagnoses were made after randomisation. As these subjects will no longer be on antiplatelet therapy, there is no need to continue with study follow up and this will be deemed as withdrawn from study participation.
Subject may withdraw his/her consent from study participation voluntarily at any time without prejudice to him/her or effect on the subject's medical care.
The Principal Investigator may stop a subject's participation in the study at any time for justified reasons. If a subject withdraws voluntarily from participation in the study for any reason, the data that have been collected until the time of his/her withdrawal will be kept and analysed. The reason is to enable a complete and comprehensive evaluation of the study. Standard medical care will continue for all subjects who withdrew from the study.
- Conditions
- Ischemic Stroke, Transient Ischemic Attack
- Being tested
- Genetic testing
- Keywords
- Genotype Guided Antiplatelet Therapy
- Medical subject headings
- Ischemic Stroke, Ischemic Attack, Transient
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic testingGenetic
Also called Testing of CYP2C19 LOF mutations
Same information as details in the experimental arm.
| Study group | Role | What they receive |
|---|---|---|
| Genetic testing | Experimental | Patients randomised to testing will have blood drawn for testing of CYP2C19 LOF mutations. Physicians of patients who test positive for an LOF mutation (intermediate and poor metabolizers) will be notified of the mutation with recommendations of possible alternative antiplatelet regimens suggested. Aspirin will be the recommended monotherapy, and aspirin in combination with ticagrelor or dipyridamole will be the recommended dual antiplatelet regimen. Decision of alternative medications used in patients with LOF mutations will be left to the discretion of the primary physician. Patients in the genotype guided antiplatelet therapy group who do not have LOF mutations will be left to continue the original intended antiplatelet regimen (this may be clopidogrel monotherapy, or in combination with aspirin).
No randomisation for patients with known CYP2C19 status prior to recruitment as these patients will be recruited as a comparison arm for outcomes measurements. Receives: Genetic: Genetic testing |
| Standard medical therapy | No intervention | Patients on this arm will be placed on clopidogrel monotherapy, or in combination with aspirin, which is the original intended antiplatelet regimen. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major adverse cardiovascular or cerebrovascular events (MACCE) over 12 months following the index stroke
MACCE includes either death, myocardial infarction, stent thrombosis, admission for acute coronary syndrome / unstable angina, ischemic cerebrovascular accident or transient ischemic event.
Measured: 12 months
Secondary outcomes (1)
Clinically significant bleeding
Defined as a GUSTO moderate or severe / life threatening bleeding event.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2023
- Study start24 Apr 2023
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multicentre, prospective, randomised, open blinded endpoint trial.
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Neuroscience Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Singapore General Hospital
- Responsible party
- Sponsor
- Investigators
- Kaavya Narasimhalu, Principal investigator, National Neuroscience Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05763862
- Sponsor's protocol ID
- GGAT Protocol
- Status last verified
- Nov 2025
- First submitted
- 28 Feb 2023
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lovett JK, Coull AJ, Rothwell PM. Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology. 2004 Feb 24;62(4):569-73. doi: 10.1212/01.wnl.0000110311.09970.83.
PubMed 14981172Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence. Stroke. 2000 May;31(5):1062-8. doi: 10.1161/01.str.31.5.1062.
PubMed 10797166Purroy F, Montaner J, Molina CA, Delgado P, Ribo M, Alvarez-Sabin J. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007 Dec;38(12):3225-9. doi: 10.1161/STROKEAHA.107.488833. Epub 2007 Oct 25.
PubMed 17962602CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.
PubMed 8918275Wang Y, Zhao X, Lin J, Li H, Johnston SC, Lin Y, Pan Y, Liu L, Wang D, Wang C, Meng X, Xu J, Wang Y; CHANCE investigators. Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack. JAMA. 2016 Jul 5;316(1):70-8. doi: 10.1001/jama.2016.8662.
PubMed 27348249Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-225. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16.
PubMed 29766750Humbert M, Nurden P, Bihour C, Pasquet JM, Winckler J, Heilmann E, Savi P, Herbert JM, Kunicki TJ, Nurden AT. Ultrastructural studies of platelet aggregates from human subjects receiving clopidogrel and from a patient with an inherited defect of an ADP-dependent pathway of platelet activation. Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1532-43. doi: 10.1161/01.atv.16.12.1532.
PubMed 8977459Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, Klein TE, Sabatine MS, Johnson JA, Shuldiner AR; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013 Sep;94(3):317-23. doi: 10.1038/clpt.2013.105. Epub 2013 May 22.
PubMed 23698643Goh LL, Lim CW, Sim WC, Toh LX, Leong KP. Analysis of Genetic Variation in CYP450 Genes for Clinical Implementation. PLoS One. 2017 Jan 3;12(1):e0169233. doi: 10.1371/journal.pone.0169233. eCollection 2017.
PubMed 28046094Meschia JF, Walton RL, Farrugia LP, Ross OA, Elm JJ, Farrant M, Meurer WJ, Lindblad AS, Barsan W, Ching M, Gentile N, Ross M, Nahab F, Easton JD, Kim AS, Zurita KG, Cucchiara B, Johnston SC. Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial. Stroke. 2020 Jul;51(7):2058-2065. doi: 10.1161/STROKEAHA.119.028713. Epub 2020 Jun 17.
PubMed 32568642Narasimhalu K, Ang YK, Tan DSY, De Silva DA, Tan KB. Cost Effectiveness of Genotype-Guided Antiplatelet Therapy in Asian Ischemic Stroke Patients: Ticagrelor as an Alternative to Clopidogrel in Patients with CYP2C19 Loss of Function Mutations. Clin Drug Investig. 2020 Nov;40(11):1063-1070. doi: 10.1007/s40261-020-00970-y.
PubMed 32959334Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
PubMed 21670242Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y; THALES Investigators. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870.
PubMed 32668111Gaglia MA, Torguson R, Pakala R, Xue Z, Sardi G, Suddath WO, Kent KM, Satler LF, Pichard AD, Waksman R. Correlation between light transmission aggregometry, VerifyNow P2Y12, and VASP-P platelet reactivity assays following percutaneous coronary intervention. J Interv Cardiol. 2011 Dec;24(6):529-34. doi: 10.1111/j.1540-8183.2011.00670.x. Epub 2011 Sep 15.
PubMed 21919956Lee CR, Sriramoju VB, Cervantes A, Howell LA, Varunok N, Madan S, Hamrick K, Polasek MJ, Lee JA, Clarke M, Cicci JD, Weck KE, Stouffer GA. Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. Circ Genom Precis Med. 2018 Apr;11(4):e002069. doi: 10.1161/CIRCGEN.117.002069.
PubMed 29615454
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype Guided Antiplatelet Therapy In Ischemic Stroke
- ClinicalTrials.gov ID
- NCT05763862
- Acronym / sponsor ID
- GGAT Protocol
- Conditions
- Ischemic Stroke, Transient Ischemic Attack
- Keywords
- Genotype Guided Antiplatelet Therapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- National Neuroscience InstituteUniversity, hospital or other
- Collaborators
- Singapore General Hospital
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 10 Mar 2023 (actual)
- 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.
A fifth of ischemic stroke or transient ischemic attack (TIA) patients will have recurrent events within the first 3 months [Refs 1-3] despite aggressive medical therapy with antiplatelets and risk factor control.
Clopidogrel is one of the mainstays of antiplatelet secondary prevention therapy in patients with ischemic stroke. CYP2C19 loss of function (LOF) mutations impair the effectiveness of clopidogrel [Ref 4]. The prevalence of LOF mutations is approximately 60% in the local population [Ref 5], rendering the effectiveness of empiric clopidogrel treatment doubtful. For patients who have LOF mutations, other treatment options for secondary prevention of ischemic stroke need to be tested. This study aims to determine the feasibility and clinical impact of genetic testing guided antiplatelet therapy in ischemic stroke patients on the prevention of major adverse cardiovascular or cerebrovascular events.
Clopidogrel naive ischemic stroke or TIA patients aged 21 years and above will be randomised to genetic testing guided antiplatelet therapy or standard medical therapy within 7 days of their index event. Patients allocated to testing group will have blood sample drawn for diagnosis of CYP2C19 LOF mutations. Patients who test positive for an LOF mutation (intermediate and poor metabolisers) will be offered alternative antiplatelet therapy in the form of aspirn (for those who need monotherapy) or aspirin plus ticagrelor or dipyridamole (for those who need dual antiplatelet therapy) to be decided by the managing physician. Patients who test negative for LOF mutation will continue on clopidogrel. Platelet reactivity index (enables the identification of patients with an inadequate response to antiplatelet agents) will be measured at baseline.
Detailed description
This is a multicentre, prospective, randomised, open blinded endpoint trial.
The study will include three visits: Baseline (within 1 week of index event), 3 months, and 12 months. Randomisation will be performed for patients with unknown CYP2C19 status while no randomisation will be done for patients with known CYP2C19 status at the time of recruitment. Baseline visit will need to be in-person, whle the 3-month and 12-month follow-ups can either be inperson or via telephone. Data on antiplatelet regimen, MACCE outcomes, and GUSTO outcomes will be collected at the follow-up visits. Blood tests will be performed on the genetic testing guided antiplatelet therapy arm and standard medical therapy arm at baseline to determine the platelet reactivity index (PRI).
Patients with unknown CYP2C19 status will be randomised to genetic testing versus standard medical therapy in a 1:1 ratio, via a block randomisation process. The block randomisation sequence will be generated by a web-based randomisation service in blocks of four for each recruitment site. Blinding is not applicable for the treatment assigned.
Patients randomised to testing will have blood drawn for testing of the CYP2C19 LOF mutations. Physicians of patients who test positive for an LOF mutation (intermediate and poor metabolizers) will be notified of the mutation with recommendations of possible alternative antiplatelet regimens suggested. Aspirin will be the recommended monotherapy, and aspirin in combination with ticagrelor or dipyridamole will be the recommended dual antiplatelet regimen. The decision of alternative medications used in patients with LOF mutations will be left to the discretion of the primary physician. Patients in the standard medical therapy group, and patients in the genotype guided antiplatelet therapy group who do not have LOF mutations (normal metabolisers) will be left to continue the original intended antiplatelet regimen - this may be clopidogrel monotherapy, or in combination with aspirin. Patients who experience recurrent events during follow-up, or who have drug intolerance can be changed from the antiplatelet regimen as per primary physician's discretion. Information on all medications, including antiplatelet regimen at discharge and at subsequent reviews will be collected.
There will be no randomisation for patients with known CYP2C19 status prior to recruitment. Patients with known CYP2C19 status will be recruited as a comparison arm for outcomes measurements.
CYP2C19 genotyping will be performed by the Singapore General Hospital's clinical laboratory services. Turnaround time for CYP2C19 is approximately 7 days. Patient will be notified of CYP2C10 LOF mutation result.
Demographic characteristics that will be ascertained includes age, sex, ethnicity, education level, date of study randomisation. Past medical history will be recorded: hypertension, diabetes, hyperlipidemia, ischemic heart disease, atrial fibrillation, smoking, peripheral vascular disease, previous ischemic stroke/transient ischemic attack, intracranial bleeding, clinically significant bleeding, smoking and alcohol. Information pertaining to hospital admission, stroke characteristics, medications that the patients are on, particularly antiplatelet, anticoagulation, proton pump inhibitor, histamine H2 receptor antagonists, and cardiovascular medication prior to the admission and at discharge will be assessed. Use of single versus dual antiplatelet therapy, and duration of dual antiplatelet therapy will be considered confounders.
For subjects randomised to the standard medical therapy arm, genetic testing for CYP2C19 LOF mutations may be performed for clinical purpose after randomisation and before the end of subject's participation in the study, which could result in treatment changes. Such cases will not be considered as a protocol violation. These subjects will continue with treatment as per advised by the primary physician and may continue study follow ups till the end of the study.
If subjects are identified after randomisation to have cardioembolism or prothrombotic state necessitating the use of anticoagulation, the treating physician should manage as per standard medical care. These will not be considered as protocol violation as the diagnoses were made after randomisation. As these subjects will no longer be on antiplatelet therapy, there is no need to continue with study follow up and this will be deemed as withdrawn from study participation.
Subject may withdraw his/her consent from study participation voluntarily at any time without prejudice to him/her or effect on the subject's medical care.
The Principal Investigator may stop a subject's participation in the study at any time for justified reasons. If a subject withdraws voluntarily from participation in the study for any reason, the data that have been collected until the time of his/her withdrawal will be kept and analysed. The reason is to enable a complete and comprehensive evaluation of the study. Standard medical care will continue for all subjects who withdrew from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a multicentre, prospective, randomised, open blinded endpoint trial.
| Arm | Type | Receives |
|---|---|---|
| Genetic testing | Experimental | Genetic: Genetic testingPatients randomised to testing will have blood drawn for testing of CYP2C19 LOF mutations. Physicians of patients who test positive for an LOF mutation (intermediate and poor metabolizers) will be notified of the mutation with recommendations of possible alternative antiplatelet regimens suggested. Aspirin will be the recommended monotherapy, and aspirin in combination with ticagrelor or dipyridamole will be the recommended dual antiplatelet regimen. Decision of alternative medications used in patients with LOF mutations will be left to the discretion of the primary physician. Patients in the genotype guided antiplatelet therapy group who do not have LOF mutations will be left to continue the original intended antiplatelet regimen (this may be clopidogrel monotherapy, or in combination with aspirin). No randomisation for patients with known CYP2C19 status prior to recruitment as these patients will be recruited as a comparison arm for outcomes measurements. |
| Standard medical therapy | No intervention | –Patients on this arm will be placed on clopidogrel monotherapy, or in combination with aspirin, which is the original intended antiplatelet regimen. |
Who may qualify
- Ages
- 21 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients diagnosed with acute ischemic stroke or transient ischemic attack.
- Age 21 years to 100 years.
- Can be randomised within 7 days of onset of index event [Refer to footnote 1].
- Clopidogrel naive immediately prior to index event [Refer to footnote 2].
- Footnote 1: Date of index event to be taken as Day 1. This means that randomisation must be done by Day 7. For unknown onset or wake-up stroke where the last seen well and symptoms discovery are on different days, Day 1 is taken to be the date of symptoms discovery. Footnote 2: Patients who were on short-term antiplatelets which included clopidogrel but are no longer on clopidogrel prior to stroke would fulfil for this inclusion criteria. In this context, short-term antiplatelets are defined as 21 days for minor stroke TIA and 3 months for large vessel disease.
Key exclusion criteria (4 listed)
- Known diagnosis of dementia [Refer to footnote 3].
- Known diagnosis of a life limiting illness with life expectancy of less than 1 year.
- Known cardioembolism or prothrombotic state necessitating the use of anticoagulation, or having a contraindication to clopidogrel.
- Footnote 3: "Known diagnosis of dementia" will be defined as clinical diagnosis of dementia prior to the index stroke event as indicated in the patient's medical records.
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 |
|---|---|---|
| Genetic testingAlso: Testing of CYP2C19 LOF mutationsSame information as details in the experimental arm. | Genetic | Genetic testing |
Primary outcome
Major adverse cardiovascular or cerebrovascular events (MACCE) over 12 months following the index stroke
Time frame: 12 months
MACCE includes either death, myocardial infarction, stent thrombosis, admission for acute coronary syndrome / unstable angina, ischemic cerebrovascular accident or transient ischemic event.
1 secondary outcome
Clinically significant bleeding
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Background: PubMed 14981172Lovett JK, Coull AJ, Rothwell PM. Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology. 2004 Feb 24;62(4):569-73. doi: 10.1212/01.wnl.0000110311.09970.83.
- Background: PubMed 10797166Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence. Stroke. 2000 May;31(5):1062-8. doi: 10.1161/01.str.31.5.1062.
- Background: PubMed 17962602Purroy F, Montaner J, Molina CA, Delgado P, Ribo M, Alvarez-Sabin J. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007 Dec;38(12):3225-9. doi: 10.1161/STROKEAHA.107.488833. Epub 2007 Oct 25.
- Background: PubMed 8918275CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.
- Background: PubMed 27348249Wang Y, Zhao X, Lin J, Li H, Johnston SC, Lin Y, Pan Y, Liu L, Wang D, Wang C, Meng X, Xu J, Wang Y; CHANCE investigators. Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack. JAMA. 2016 Jul 5;316(1):70-8. doi: 10.1001/jama.2016.8662.
- Background: PubMed 29766750Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-225. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16.
- Background: PubMed 8977459Humbert M, Nurden P, Bihour C, Pasquet JM, Winckler J, Heilmann E, Savi P, Herbert JM, Kunicki TJ, Nurden AT. Ultrastructural studies of platelet aggregates from human subjects receiving clopidogrel and from a patient with an inherited defect of an ADP-dependent pathway of platelet activation. Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1532-43. doi: 10.1161/01.atv.16.12.1532.
- Background: PubMed 23698643Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, Klein TE, Sabatine MS, Johnson JA, Shuldiner AR; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013 Sep;94(3):317-23. doi: 10.1038/clpt.2013.105. Epub 2013 May 22.
- Background: PubMed 28046094Goh LL, Lim CW, Sim WC, Toh LX, Leong KP. Analysis of Genetic Variation in CYP450 Genes for Clinical Implementation. PLoS One. 2017 Jan 3;12(1):e0169233. doi: 10.1371/journal.pone.0169233. eCollection 2017.
- Background: PubMed 32568642Meschia JF, Walton RL, Farrugia LP, Ross OA, Elm JJ, Farrant M, Meurer WJ, Lindblad AS, Barsan W, Ching M, Gentile N, Ross M, Nahab F, Easton JD, Kim AS, Zurita KG, Cucchiara B, Johnston SC. Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial. Stroke. 2020 Jul;51(7):2058-2065. doi: 10.1161/STROKEAHA.119.028713. Epub 2020 Jun 17.
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- Background: PubMed 21670242Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
- Individual participant dataSharing planned: No
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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.
Kaavya Narasimhalu principal investigator
National Neuroscience Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Genetic testing in people with Ischemic Stroke and Transient Ischemic Attack, run by National Neuroscience Institute at 1 site in Singapore.
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 5 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 16 Apr 2026. 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 Singapore. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Major adverse cardiovascular or cerebrovascular events (MACCE) over 12 months following the index stroke (time frame: 12 months). 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 NCT05763862, which also lists 16 linked publications.
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 16 Apr 2026.