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THALES - Acute STroke or Transient IscHaemic Attack Treated With TicAgreLor and ASA for PrEvention of Stroke and Death (THALES)

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ClinicalTrials.gov Identifier: NCT03354429
Recruitment Status : Recruiting
First Posted : November 28, 2017
Last Update Posted : June 28, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief 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

Condition or disease Intervention/treatment Phase
Acute Ischaemic Stroke Transient Ischaemic Attack Drug: Ticagrelor Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blind, Placebo-Controlled, International, Multicentre, Phase III Study to Investigate the Efficacy and Safety of Ticagrelor and ASA Compared With ASA in the Prevention of Stroke and Death in Patients With Acute Ischaemic Stroke or Transient Ischaemic Attack
Actual Study Start Date : January 22, 2018
Estimated Primary Completion Date : December 16, 2019
Estimated Study Completion Date : December 16, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arm Intervention/treatment
Experimental: TICAGRELOR Drug: Ticagrelor
Ticagrelor arm: Day 1, loading dose of ticagrelor followed by daily maintenance dose until Day 30.

Placebo Comparator: TICAGRELOR PLACEBO Drug: Placebo
Placebo arm: Day 1, loading dose of placebo followed by placebo daily maintenance dose until Day 30.




Primary Outcome Measures :
  1. Time from randomisation to first subsequent stroke or death [ Time Frame: Day1-Day30 ]
    To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in AIS/TIA patients in the prevention of the composite of stroke and death at 30 days


Secondary Outcome Measures :
  1. Time from randomisation to first subsequent ischaemic stroke [ Time Frame: Day1-Day30 ]
    To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in AIS/TIA patients in the prevention of ischaemic stroke at 30 days

  2. The modified Rankin Scale (mRS) score >1 at Visit 3 [ Time Frame: Day30 ]
    To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in AIS/TIA patients in reducing overall disability at 30 days. The modified Rankin Scale (mRS) is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death.0 - No symptoms,1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.


Other Outcome Measures:
  1. Time from randomisation to first bleeding event that fulfils SAE criteria and is categorised as GUSTO Severe [ Time Frame: Day1-Day30 ]
    To assess the safety of ticagrelor and ASA compared with that of placebo and ASA in AIS/TIA patients, in particular with respect to major bleeding events

  2. Time from randomisation to first ICH or fatal bleeding event [ Time Frame: Day1-Day30 ]
    To assess the safety of ticagrelor and ASA compared with that of placebo and ASA in AIS/TIA patients, in particular with respect to major bleeding events

  3. Time from randomisation to first bleeding event that fulfils SAE criteria and is categorised as GUSTO Moderate/Severe [ Time Frame: Day1-Day30 ]
    To assess the safety of ticagrelor and ASA compared with that of placebo and ASA in AIS/TIA patients, in particular with respect to major bleeding events

  4. Time from randomisation to premature permanent discontinuation of IP due to bleeding [ Time Frame: Day1-Day30 ]
    To assess the safety of ticagrelor and ASA compared with that of placebo and ASA in AIS/TIA patients, in particular with respect to major bleeding events



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03354429


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 391 Study Locations
Sponsors and Collaborators
AstraZeneca

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03354429     History of Changes
Other Study ID Numbers: D5134C00003
2016-004232-37 ( EudraCT Number )
First Posted: November 28, 2017    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AstraZeneca:
Acute ischaemic stroke; Transient Ischaemic Attack (TIA); Stroke

Additional relevant MeSH terms:
Ischemic Attack, Transient
Stroke
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs