THALES - Acute STroke or Transient IscHaemic Attack Treated With TicAgreLor and ASA for PrEvention of Stroke and Death
Condition: Acute Ischaemic Stroke; Transient Ischaemic Attack
MeSH terms: Stroke; Ischemic Stroke; Ischemic Attack, Transient; Ischemia
Intervention: Ticagrelor; Placebo
Intervention description: Ticagrelor arm: Day 1, loading dose of ticagrelor followed by daily maintenance dose until Day 30.; Placebo arm: Day 1, loading dose of placebo followed by placebo daily maintenance dose until Day 30.
Intervention MeSH terms: Ticagrelor
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11016.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Acute ischaemic stroke; Transient Ischaemic Attack (TIA); Stroke

Summary:

      Study to investigate if the study drug ticagrelor and ASA is more effective than Placebo
      (inactive tablet) and ASA in preventing new stroke events
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed informed consent prior to any study-specific procedure

          2. ≥40 years of age

          3. Acute onset of cerebral ischaemia due to

               1. AIS with NIHSS ≤5. AIS is defined as acute onset of neurological deficit
                  attributed to focal brain ischaemia, and either of the following:

                    -  Persistent signs or symptoms of the ischaemic event at the time o
                       randomisation, OR

                    -  Acute ischaemic brain lesion documented before randomisation by computed
                       tomography (CT) scan or magnetic resonance imaging (MRI) (diffusion-weighted
                       imaging) and that could account for the clinical presentation

               2. High-risk TIA, defined as neurological deficit of acute onset attributed to focal
                  ischaemia of the brain by history or examination with complete resolution of the
                  deficit, and at least one of the following:

                    -  ABCD2 score ≥6 and TIA symptoms not limited to isolated numbness, isolated
                       visual changes, or isolated dizziness/vertigo

                    -  Symptomatic intracranial arterial occlusive disease that could account for
                       the clinical presentation, documented by transcranial Doppler or vascular
                       imaging and defined as at least 50% narrowing in the diameter of the vessel
                       lumen

                    -  Internal carotid arterial occlusive disease that could account for the
                       clinical presentation, documented by Doppler, ultrasound, or vascular
                       imaging and defined as at least 50% narrowing in diameter of the vessel
                       lumen

          4. Randomisation occurring within 24 hours after onset of symptoms; for wake-up strokes
             (when the time of symptom onset is not known), within 24 hours from the time point at
             which the patient was reported to be in their normal condition

          5. CT or MRI performed after symptom onset ruling out intracranial haemorrhage or other
             pathology, such as vascular malformation, tumour, or abscess that according

        to the Investigator could explain symptoms or contraindicate study treatment

        Exclusion Criteria:

          1. Need for or an anticipated need for any of the following:

               1. Dual antiplatelet therapy with ASA and P2Y12 inhibitors (including patients with
                  carotid artery stenting and percutaneous coronary intervention)

               2. Antiplatelets other than ASA (eg, GPIIb/IIIa inhibitors, clopidogrel,
                  ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol, ticagrelor) and other
                  antithrombotic agents with antiplatelet effects, including traditional/herbal
                  medicine agents

               3. Anticoagulants (eg, warfarin, oral thrombin and factor Xa inhibitors,
                  bivalirudin, hirudin, argatroban, fondaparinux, or unfractionated heparin and
                  long-term treatment with low-molecular weight heparins). Short-term treatment (≤7
                  days) with low-dose low-molecular weight heparin may be used in immobilised
                  patients at the discretion of the Investigator

          2. Any history of atrial fibrillation/flutter, ventricular aneurysm, or suspicion of
             other cardioembolic pathology for TIA or stroke

          3. Patients who should receive or have received any intravenous or intra-arterial
             thrombolysis or mechanical thrombectomy within 24 hours prior to randomisation

          4. Planned carotid endarterectomy that requires halting investigational product within 3
             days of randomisation or is expected to require unblinding of investigational product
             (planned carotid endarterectomy is in itself not an exclusion criterion)

          5. History of previous intracranial haemorrhage at any time (asymptomatic microbleeds do
             not qualify), gastrointestinal haemorrhage within the past 6 months, or major surgery
             within 30 days

          6. Patients considered to be at risk of bradycardic events (eg, known sick sinus syndrome
             or second- or third-degree atrioventricular block) unless already treated with a
             permanent pacemaker

          7. Inability of the patient to understand and/or comply with study procedures and/or
             follow-up, in the opinion of the Investigator

          8. Known hypersensitivity to ticagrelor or ASA

          9. Need for or an anticipated need for oral or intravenous therapy with any of the
             following:

               1. Strong cytochrome P450 3A (CYP3A4) inhibitors (eg, ketoconazole, clarithromycin
                  [but not erythromycin or azithromycin], nefazadone, ritonavir, atazanavir) that
                  cannot be stopped for the course of the study

               2. Long-term (>7 days) non-steroidal anti-inflammatory drugs

         10. Known bleeding diathesis or coagulation disorder (eg, thrombotic thrombocytopenic
             purpura)

         11. Known severe liver disease (eg, ascites or signs of coagulopathy)

         12. Renal failure requiring dialysis

         13. Pregnancy or breastfeeding. Women of child-bearing potential who are not willing to
             use a medically accepted method of contraception that is considered reliable in the
             judgment of the Investigator

         14. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site)

         15. Previous enrolment or randomisation in the present study

         16. Participation in another clinical study with an investigational product at any time
             during the 30 days prior to randomisation (regardless of when treatment with the
             investigational product was discontinued)