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

Acute Ischaemic Stroke Clinical Trial

— THALES  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03354429
• Other study ID #: D5134C00003
• Secondary ID: 2016-004232-37
• Status: Completed
• Phase: Phase 3
• Start date: January 22, 2018
• Est. completion date: December 13, 2019

Study information

• Verified date: December 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11016
• Est. completion date: December 13, 2019
• Est. primary completion date: December 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 130 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Ischaemic Stroke
• Ischemia
• Ischemic Attack, Transient
• Stroke
• Transient Ischaemic Attack

Intervention

Drug:
• Ticagrelor
Ticagrelor arm: Day 1, loading dose of ticagrelor followed by daily maintenance dose until Day 30.
• Placebo
Placebo arm: Day 1, loading dose of placebo followed by placebo daily maintenance dose until Day 30.

Locations

Country	Name	City	State
Argentina	Research Site	Adrogué
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Capital Federal
Argentina	Research Site	Ciudad Autónoma de Bs. As.
Argentina	Research Site	Cordoba
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	Salta
Australia	Research Site	Adelaide
Australia	Research Site	Heidelberg
Australia	Research Site	Herston
Australia	Research Site	Parkville
Australia	Research Site	Southport
Australia	Research Site	St Albans
Belgium	Research Site	Antwerpen
Belgium	Research Site	Assebroek (Brugge)
Belgium	Research Site	Bruges
Belgium	Research Site	Brussels
Belgium	Research Site	Dendermonde
Belgium	Research Site	Edegem
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Belgium	Research Site	Oostende
Belgium	Research Site	Roeselare
Belgium	Research Site	Sint-Truiden
Belgium	Research Site	Yvoir
Brazil	Research Site	Botucatu
Brazil	Research Site	Curitiba
Brazil	Research Site	Goiania
Brazil	Research Site	Joinville
Brazil	Research Site	Maringa
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirao Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Lukovit
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Teteven
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Chicoutimi
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Lethbridge	Alberta
China	Research Site	Baoji
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chifeng
China	Research Site	Daqing
China	Research Site	Foshan
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hohhot
China	Research Site	Hohhot
China	Research Site	Jinan
China	Research Site	Jinzhou
China	Research Site	Liuzhou
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nantong
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Taiyuan
China	Research Site	Tangshan
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Wenzhou
China	Research Site	Wu Han
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Xining
China	Research Site	Xuzhou
Czechia	Research Site	Brno
Czechia	Research Site	Chomutov
Czechia	Research Site	Ostrava
Czechia	Research Site	Ostrava
Czechia	Research Site	Pardubice
Czechia	Research Site	Praha 4
Czechia	Research Site	Usti nad Labem
France	Research Site	Bayonne
France	Research Site	Besancon Cedex
France	Research Site	Bordeaux Cedex
France	Research Site	Bourg en Bresse
France	Research Site	Brest Cedex 2
France	Research Site	Caen
France	Research Site	Corbeil Essonnes Cedex
France	Research Site	Dijon
France	Research Site	Le Chesnay Cedex
France	Research Site	Lille
France	Research Site	Metz
France	Research Site	Montpellier Cedex 5
France	Research Site	Nancy
France	Research Site	NICE Cedex 01
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	PARIS Cedex 12
France	Research Site	Paris Cedex 13
France	Research Site	Paris Cedex 18
France	Research Site	Rennes
France	Research Site	Rouen Cedex
France	Research Site	Saint Herblain
France	Research Site	Saint-Priez En Jarez
France	Research Site	Strasbourg Cedex
France	Research Site	Suresnes Cedex
France	Research Site	Toulouse Cedex 9
Germany	Research Site	Altenburg
Germany	Research Site	Bad Neustadt
Germany	Research Site	Berlin
Germany	Research Site	Erlangen
Germany	Research Site	Essen
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Minden
Germany	Research Site	Münster
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Kowloon
Hungary	Research Site	Baja
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Kistarcsa
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Sopron-Balf
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Tatabánya
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Bengaluru
India	Research Site	Dehradun
India	Research Site	Guntur
India	Research Site	Gurgaon
India	Research Site	Gurgaon
India	Research Site	Hyderabad
India	Research Site	Kanpur
India	Research Site	Kolkata
India	Research Site	Mangalore
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Srikakulam
India	Research Site	Varanasi
Italy	Research Site	Cona
Italy	Research Site	Genova
Italy	Research Site	Genova
Italy	Research Site	Massa
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Negrar
Italy	Research Site	Pavia
Italy	Research Site	Perugia
Italy	Research Site	Pietra Ligure
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Siena
Italy	Research Site	Varese
Italy	Research Site	Verona
Italy	Research Site	Vicenza
Italy	Research Site	Vizzolo Predabissi
Korea, Republic of	Research Site	Anyang-si
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daejeon-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jeju-do
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Culiacan
Mexico	Research Site	D.F
Mexico	Research Site	Durango
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	Mexico City
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Mexico	Research Site	Tijuana
Peru	Research Site	Bellavista
Peru	Research Site	Callao
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Trujillo
Peru	Research Site	Urb. El Chipe
Poland	Research Site	Bialystok
Poland	Research Site	Chelm
Poland	Research Site	Dzialdowo
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Gryfice
Poland	Research Site	Katowice
Poland	Research Site	Konskie
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Olsztyn
Poland	Research Site	Ostroleka
Poland	Research Site	Rybnik
Poland	Research Site	Sandomierz
Poland	Research Site	Skarzysko-Kamienna
Poland	Research Site	Swiebodzin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Zielona Góra
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Iasi
Romania	Research Site	Oradea
Romania	Research Site	Sibiu
Romania	Research Site	Timisoara
Romania	Research Site	Tirgu-Mures
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhnii Novgorod
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Samara
Russian Federation	Research Site	Samara
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Sochi
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Voronezh
Russian Federation	Research Site	Yaroslavl
Saudi Arabia	Research Site	Ar Riya?
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Slovakia	Research Site	Dolny Kubin
Slovakia	Research Site	Levoca
Slovakia	Research Site	Liptovsky Mikulas
Slovakia	Research Site	Martin
Slovakia	Research Site	Nitra
Slovakia	Research Site	Rimavska Sobota
Slovakia	Research Site	Skalica
Slovakia	Research Site	Spisska Nova Ves
Slovakia	Research Site	Trencin
Slovakia	Research Site	Trnava
Slovakia	Research Site	Ziar nad Hronom
Spain	Research Site	Albacete
Spain	Research Site	Alicante
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Gerona
Spain	Research Site	Lleida
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valladolid
Spain	Research Site	Zaragoza
Sweden	Research Site	Göteborg
Sweden	Research Site	Linköping
Sweden	Research Site	Lund
Sweden	Research Site	Malmö
Sweden	Research Site	Ostersund
Sweden	Research Site	Skövde
Sweden	Research Site	Solna
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Taiwan	Research Site	Changhua
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Keelung
Taiwan	Research Site	New Taipei
Taiwan	Research Site	New Taipei City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung City
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan Hsien
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chonburi
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khlong Luang
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Lampang
Thailand	Research Site	Muang
Thailand	Research Site	Nakhonpathom
Thailand	Research Site	Prachinburi
Thailand	Research Site	Rajthevi
Thailand	Research Site	Ratchaburi
Thailand	Research Site	Ubonratchathani
Ukraine	Research Site	Chernivts?
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kherson
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Poltava
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhia
Ukraine	Research Site	Zaporizhzhia
Vietnam	Research Site	Dong Nai
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bleeding Event That Fulfils Serious Adverse Event Criteria and is Categorised as GUSTO Severe	Participants with bleeding event that fulfils serious adverse event criteria and is categorised as GUSTO Severe. GUSTO is a bleeding scale (GUSTO = Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries). GUSTO Severe bleeding is defined as any of the following: (1) fatal bleeding, (2) intracranial bleeding, or (3) bleeding that caused haemodynamic compromise requiring intervention	From randomisation (day 1) to visit 3 (day 30-34)
Other	ICH or Fatal Bleeding Event	Participants with ICH or fatal bleeding event	From randomisation (day 1) to visit 3 (day 30-34)
Other	Bleeding Event That Fulfils Serious Adverse Event Criteria and is Categorised as GUSTO Moderate/Severe	Participants with bleeding event that fulfils serious adverse event criteria and is categorised as GUSTO Moderate/Severe. GUSTO is a bleeding scale (GUSTO = Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries). GUSTO Severe bleeding is defined as any of the following: (1) fatal bleeding, (2) intracranial bleeding, or (3) bleeding that caused haemodynamic compromise requiring intervention. GUSTO Moderate bleeding is a bleeding requiring transfusion of whole blood or packed red blood cells without haemodynamic compromise	From randomisation (day 1) to visit 3 (day 30-34)
Other	Premature Permanent Discontinuation of IP Due to Bleeding	Participants with premature permanent discontinuation of IP due to bleeding	From randomisation (day 1) to visit 3 (day 30-34)
Primary	Composite of Subsequent Stroke or Death	Participants with subsequent stroke or death	From randomisation (day 1) to visit 3 (day 30-34)
Secondary	Ischaemic Stroke	Number of participants with ischaemic stroke	From randomisation (day 1) to visit 3 (day 30-34)
Secondary	Number of Participants With Modified Rankin Scale (mRS) Score >1 at Visit 3	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.	Visit 3 (day 30-34)

External Links

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