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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 : July 10, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE November 20, 2017
First Posted Date  ICMJE November 28, 2017
Last Update Posted Date July 10, 2019
Actual Study Start Date  ICMJE January 22, 2018
Estimated Primary Completion Date December 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 24, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03354429 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2017)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 24, 2017)
  • 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
  • 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
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE THALES - Acute STroke or Transient IscHaemic Attack Treated With TicAgreLor and ASA for PrEvention of Stroke and Death
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Ischaemic Stroke
  • Transient Ischaemic Attack
Intervention  ICMJE
  • Drug: Ticagrelor
    Ticagrelor arm: Day 1, loading dose of ticagrelor followed by daily maintenance dose until Day 30.
  • Drug: Placebo
    Placebo arm: Day 1, loading dose of placebo followed by placebo daily maintenance dose until Day 30.
Study Arms  ICMJE
  • Experimental: TICAGRELOR
    Intervention: Drug: Ticagrelor
  • Placebo Comparator: TICAGRELOR PLACEBO
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2019)
11000
Original Estimated Enrollment  ICMJE
 (submitted: November 24, 2017)
13000
Estimated Study Completion Date  ICMJE December 16, 2019
Estimated Primary Completion Date December 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Czechia,   France,   Germany,   Hong Kong,   Hungary,   India,   Italy,   Korea, Republic of,   Mexico,   Peru,   Poland,   Romania,   Russian Federation,   Saudi Arabia,   Slovakia,   Spain,   Sweden,   Taiwan,   Thailand,   Ukraine,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03354429
Other Study ID Numbers  ICMJE D5134C00003
2016-004232-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP