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

Study identifier:D5134C00003

ClinicalTrials.gov identifier:NCT03354429

EudraCT identifier:2016-004232-37

CTIS identifier:N/A

Study Complete

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

Medical condition

Acute Ischaemic Stroke, Transient ischaemic attack

Phase

Phase 3

Healthy volunteers

Study drug

Ticagrelor, Placebo

Sex

All

Actual Enrollment

11016

Study type

Interventional

Age

40 Years - 130 Years

Date

Study Start Date: 22 Jan 2018

Primary Completion Date: 13 Dec 2019

Study Completion Date: 13 Dec 2019

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2020 by AstraZeneca

Collaborators

Inclusion and exclusion 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
(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 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
(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

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 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)

No locations available

Arms	Assigned Interventions
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.

Documents available

redacted SAP
Download
redacted CSP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]