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

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2016-004232-37-SE
• Date of registration: 02/10/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Study to investigate if the study drug ticagrelor and ASA is more effective than Placebo (inactive tablet) and ASA in preventing new stroke events.
• Scientific 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 - THALES
• Date of first enrolment: 05/12/2017
• Target sample size: 11000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004232-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, 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

Contacts

• Name: Information Center
• Affiliation: AstraZeneca AB

• Name: Information Center
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1.Provision of signed informed consent prior to any study-specific procedure and the subject is judged by the investigator to have decision-making capacity, i.e. is awake, alert and oriented to person, place, time and situation.
2.=40 years of age
3.Acute onset of cerebral ischaemia due to
(a) 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 of
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
(b) 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5500

Exclusion criteria:
1.Need for or an anticipated need for any of the following:
(a) Dual antiplatelet therapy with ASA and P2Y12 inhibitors (including patients with carotid artery stenting and percutaneous coronary intervention)
(b) 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
(c) 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:
(a) 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
(b) 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 as highly effective ie, combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence.
14.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Ischaemic stroke, transient ischaemic attack
MedDRA version: 20.0 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Brilique
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ticagrelor
CAS Number: 274693-27-5
Current Sponsor code: AZD6140, AR-C126532XX
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 180-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1. 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. To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in AIS/TIA patients in reducing overall disability at 30 days

Main Objective: To demonstrate superior efficacy of ticagrelor and ASA compared with placebo and ASA in patients with acute ischaemic stroke (AIS) or TIA in the prevention of the composite of stroke and death at 30 days

Timepoint(s) of evaluation of this end point: From randomization up to 30 days

Primary end point(s): Time from randomisation to first subsequent stroke or death

Secondary Outcome(s)

Secondary end point(s): 1. Time from randomisation to first subsequent ischaemic stroke
2. mRS score >1 at Visit 3

Timepoint(s) of evaluation of this end point: 1. From randomization up to 30 days.
2. Day 30.

Secondary ID(s)

D5134C00003

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 29/11/2017
Contact: