Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy in Symptomatic ICAD

Condition(s) studied

Investigational drug(s) / intervention(s)

Point-of-Care CYP2C19 Testing: Genetic testing with the Genomadix cube to determine P2Y12 inhibitor

ticagrelor + aspirin: If patients are poor or intermediate metabolizers of clopidogrel, they will receive ticagrelor (90 mg PO BID) + aspirin (81 mg PO daily)

clopidogrel + aspirin: Normal, rapid, and ultra-rapid metabolizers of clopidogrel will receive 75 mg PO daily of clopidogrel and 81 mg PO daily of aspirin.

Study summary

Stroke is an important cause of death, disability, and memory problems in adults. The build-up of plaque in arteries inside the brain is known as "intracranial atherosclerotic disease" or "ICAD" for short, and can reduce blood flow in the brain. Clopidogrel is a medicine used to prevent strokes because it stops blood from clotting. However, there are some people who do not get as much benefit from Clopidogrel because of differences in their genes; they have a variation in a certain gene and their body is not able to properly process Clopidogrel. Another medication called Ticagrelor can benefit people who have this genetic variation. The study investigators will randomize patients who have had a stroke due to ICAD to receive genetic testing, or standard of care. The standard-of-care group will take Clopidogrel for 90 days. The genetic testing group will complete a genetic test to see if they can properly process Clopidogrel. Depending on the results of the genetic test, patients will either take Clopidogrel or Ticagrelor for 90 days. All patients will have a brain scan at baseline and 90 days to see if they had any new strokes. Patients will also complete tests and questionnaires about function and memory at baseline and 90 days. This study will be one of the first to see if it is feasible and safe to use genetic testing to help choose medications for patients who have had a stroke. This will help the study investigators design a larger study that can test if genetic testing in stroke patients reduces future stroke risk and improves health outcomes.

Eligibility

Primary outcome measure(s)

• Rate of recruitment — Through study completion, an average of 90 days
  The number of patients who provide informed consent, or are deemed ineligible after screening.
• Rate of study completion — Through study completion, an average of 90 days
  The number of patients who complete the entire study protocol
• Rate of protocol deviations — Through study completion, an average of 90 days
  The number of patients who encounter at least one protocol deviation during the study
• Proportion of patients with Symptomatic intracerebral hemorrhage (ICH) — Through study completion, an average of 90 days
  New symptomatic ICH OR worsening existing ICH with a ≥33% increase in hematoma volume AND NIHSS score increase of ≥4 points AND clinical change is thought to be attributable to ICH
• Proportion of patients with major extracranial bleeding — Through study completion, an average of 90 days
  Bleeding in a critical area or organ, including intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, intramuscular with compartment syndrome, and/or bleeding causing a drop in hemoglobulin by 20g/L or more
• Proportion of patients with non-bleeding adverse events — Through study completion, an average of 90 days
  Non-bleeding adverse events related to the study drug including dyspnea, bradyarrhythmia, and/or chest pain

Trial sites (2)

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