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

NCT ID: NCT03354429

Last Updated: 2020-12-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

11016 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-22

Study Completion Date

2019-12-13

Brief Summary

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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

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Conditions

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Acute Ischaemic Stroke Transient Ischaemic Attack

Keywords

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Acute ischaemic stroke; Transient Ischaemic Attack (TIA); Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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TICAGRELOR

Group Type EXPERIMENTAL

Ticagrelor

Intervention Type DRUG

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

TICAGRELOR PLACEBO

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Ticagrelor

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

40 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Adrogué, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Capital Federal, , Argentina

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Ciudad Autónoma de Bs. As., , Argentina

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Córdoba, , Argentina

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Mar del Plata, , Argentina

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Mendoza, , Argentina

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Rosario, , Argentina

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Rosario, , Argentina

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Salta, , Argentina

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Adelaide, , Australia

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Heidelberg, , Australia

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Herston, , Australia

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Parkville, , Australia

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Southport, , Australia

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St Albans, , Australia

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Antwerp, , Belgium

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Assebroek (Brugge), , Belgium

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Bruges, , Belgium

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Brussels, , Belgium

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Dendermonde, , Belgium

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Edegem, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Ostend, , Belgium

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Roeselare, , Belgium

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Sint-Truiden, , Belgium

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Yvoir, , Belgium

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Botucatu, , Brazil

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Curitiba, , Brazil

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Goiânia, , Brazil

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Joinville, , Brazil

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Maringá, , Brazil

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

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Rio de Janeiro, , Brazil

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Salvador, , Brazil

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Dupnitsa, , Bulgaria

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Kozloduy, , Bulgaria

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Lukovit, , Bulgaria

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Pazardzhik, , Bulgaria

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Pleven, , Bulgaria

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Sliven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Teteven, , Bulgaria

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Lethbridge, Alberta, Canada

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Chicoutimi, , Canada

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Baoji, , China

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Baotou, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Changsha, , China

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Changsha, , China

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Changsha, , China

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Chifeng, , China

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Daqing, , China

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Foshan, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guiyang, , China

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Haikou, , China

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Hangzhou, , China

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Hohhot, , China

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Hohhot, , China

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Jinan, , China

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Jinzhou, , China

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Liuzhou, , China

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Nanchang, , China

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Nanjing, , China

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Nantong, , China

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Ningbo, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Taiyuan, , China

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Tangshan, , China

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Tianjin, , China

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Tianjin, , China

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Wenzhou, , China

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Wuhan, , China

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Wuhan, , China

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Wuhan, , China

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Wuxi, , China

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Xi'an, , China

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Xiamen, , China

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Xining, , China

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Xuzhou, , China

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Brno, , Czechia

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Chomutov, , Czechia

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Ostrava, , Czechia

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Ostrava, , Czechia

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Pardubice, , Czechia

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Prague, , Czechia

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Ústí nad Labem, , Czechia

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Bayonne, , France

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Besançon, , France

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Bordeaux, , France

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Bourg-en-Bresse, , France

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Brest, , France

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Caen, , France

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Corbeil-Essonnes, , France

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Dijon, , France

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Le Chesnay, , France

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Lille, , France

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Metz, , France

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Montpellier, , France

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Nancy, , France

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Nice, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Rennes, , France

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Rouen, , France

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Saint-Herblain, , France

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Saint-Priez En Jarez, , France

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Strasbourg, , France

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Suresnes, , France

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Toulouse, , France

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Altenburg, , Germany

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Bad Neustadt an der Saale, , Germany

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Berlin, , Germany

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Erlangen, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Minden, , Germany

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Münster, , Germany

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Hong Kong, , Hong Kong

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Kowloon, , Hong Kong

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Baja, , Hungary

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Balassagyarmat, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kistarcsa, , Hungary

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Miskolc, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Sopron-Balf, , Hungary

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Székesfehérvár, , Hungary

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Tatabánya, , Hungary

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Bangalore, , India

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Bangalore, , India

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Bengaluru, , India

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Dehradun, , India

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Guntur, , India

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Gurgaon, , India

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Gurgaon, , India

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Hyderabad, , India

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Kanpur, , India

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Kolkata, , India

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Mangalore, , India

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Nagpur, , India

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Nagpur, , India

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Nashik, , India

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New Delhi, , India

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New Delhi, , India

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New Delhi, , India

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Srikakulam, , India

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Varanasi, , India

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Cona, , Italy

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Genova, , Italy

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Genova, , Italy

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Massa, , Italy

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Milan, , Italy

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Modena, , Italy

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Negrar, , Italy

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Pavia, , Italy

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Perugia, , Italy

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Pietra Ligure, , Italy

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Pisa, , Italy

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Roma, , Italy

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Roma, , Italy

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Roma, , Italy

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Siena, , Italy

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Varese, , Italy

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Verona, , Italy

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Vicenza, , Italy

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Vizzolo Predabissi, , Italy

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Culiacán, , Mexico

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D.F, , Mexico

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Durango, , Mexico

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Guadalajara, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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México, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Tijuana, , Mexico

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Bellavista, , Peru

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Callao, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Trujillo, , Peru

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Urb. El Chipe, , Peru

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Bialystok, , Poland

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Chełm, , Poland

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Działdowo, , Poland

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Gdansk, , Poland

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Gdansk, , Poland

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Gmina Końskie, , Poland

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Gmina Świebodzin, , Poland

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Grodzisk Mazowiecki, , Poland

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Gryfice, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Olsztyn, , Poland

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Olsztyn, , Poland

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Ostrołęka, , Poland

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Rybnik, , Poland

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Sandomierz, , Poland

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Skarżysko-Kamienna, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Zielona Góra, , Poland

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Iași, , Romania

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Oradea, , Romania

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Sibiu, , Romania

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Târgu Mureş, , Romania

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Timișoara, , Romania

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Chelyabinsk, , Russia

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Izhevsk, , Russia

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Kazan', , Russia

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Kazan', , Russia

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Kemerovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Samara, , Russia

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Saratov, , Russia

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Sochi, , Russia

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Tomsk, , Russia

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Ufa, , Russia

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Voronezh, , Russia

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Yaroslavl, , Russia

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Yekaterinburg, , Russia

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Jeddah, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Dolný Kubín, , Slovakia

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Levoča, , Slovakia

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Liptovský Mikuláš, , Slovakia

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Martin, , Slovakia

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Nitra, , Slovakia

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Rimavská Sobota, , Slovakia

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Skalica, , Slovakia

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Spišská Nová Ves, , Slovakia

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Trenčín, , Slovakia

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Trnava, , Slovakia

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Žiar nad Hronom, , Slovakia

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Anyang-si, , South Korea

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Busan, , South Korea

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Busan, , South Korea

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Cheongju-si, , South Korea

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Daegu, , South Korea

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Daegu, , South Korea

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Daegu, , South Korea

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Daejeon, , South Korea

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Goyang-si, , South Korea

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Gwangju, , South Korea

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Incheon, , South Korea

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Jeju-do, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Albacete, , Spain

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Alicante, , Spain

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Badalona(Barcelona), , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Girona, , Spain

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Lleida, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valladolid, , Spain

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Zaragoza, , Spain

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Gothenburg, , Sweden

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Linköping, , Sweden

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Lund, , Sweden

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Malmo, , Sweden

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Östersund, , Sweden

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Skövde, , Sweden

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Solna, , Sweden

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Stockholm, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Changhua, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Keelung, , Taiwan

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New Taipei City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan Hsien, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chon Buri, , Thailand

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Hat Yai, , Thailand

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Khlong Luang, , Thailand

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Khon Kaen, , Thailand

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Lampang, , Thailand

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Muang, , Thailand

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Nakhonpathom, , Thailand

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Prachinburi, , Thailand

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Rajthevi, , Thailand

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Ratchaburi, , Thailand

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Ubonratchathani, , Thailand

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Chernivtsі, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv Region, , Ukraine

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Kharkiv Region, , Ukraine

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Kherson, , Ukraine

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Kyiv, , Ukraine

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Lutsk, , Ukraine

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Lviv, , Ukraine

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Poltava, , Ukraine

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Ternopil, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhia, , Ukraine

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Zaporizhzhia, , Ukraine

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Hanoi, , Vietnam

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Hà Nội, , Vietnam

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Ho Chi Minh City, , Vietnam

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Đông Nãi, , Vietnam

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Countries

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Argentina Australia Belgium Brazil Bulgaria Canada China Czechia France Germany Hong Kong Hungary India Italy Mexico Peru Poland Romania Russia Saudi Arabia Slovakia South Korea Spain Sweden Taiwan Thailand Ukraine Vietnam

References

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Tank A, Johnston SC, Jain R, Amarenco P, Mellstrom C, Rikner K, Denison H, Ladenvall P, Knutsson M, Himmelmann A, Evans SR, James S, Molina CA, Wang Y, Ouwens M. Cost-effectiveness of ticagrelor plus aspirin versus aspirin in acute ischaemic stroke or transient ischaemic attack: an economic evaluation of the THALES trial. BMJ Neurol Open. 2023 Aug 24;5(2):e000478. doi: 10.1136/bmjno-2023-000478. eCollection 2023.

Reference Type DERIVED
PMID: 37637218 (View on PubMed)

Johnston SC, Amarenco P, Aunes M, Denison H, Evans SR, Himmelmann A, Jahreskog M, James S, Knutsson M, Ladenvall P, Molina CA, Nylander S, Rother J, Wang Y; THALES Investigators. Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack. Stroke. 2021 Nov;52(11):3482-3489. doi: 10.1161/STROKEAHA.121.035555. Epub 2021 Sep 3.

Reference Type DERIVED
PMID: 34477459 (View on PubMed)

Wang Y, Pan Y, Li H, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Birve F, Ladenvall P, Molina CA, Johnston SC; THALES Steering Committee and Investigators. Efficacy and Safety of Ticagrelor and Aspirin in Patients With Moderate Ischemic Stroke: An Exploratory Analysis of the THALES Randomized Clinical Trial. JAMA Neurol. 2021 Sep 1;78(9):1091-1098. doi: 10.1001/jamaneurol.2021.2440.

Reference Type DERIVED
PMID: 34244703 (View on PubMed)

Yaghi S, de Havenon A, Rostanski S, Kvernland A, Mac Grory B, Furie KL, Kim AS, Easton JD, Johnston SC, Henninger N. Carotid Stenosis and Recurrent Ischemic Stroke: A Post-Hoc Analysis of the POINT Trial. Stroke. 2021 Jul;52(7):2414-2417. doi: 10.1161/STROKEAHA.121.034089. Epub 2021 May 4.

Reference Type DERIVED
PMID: 33940954 (View on PubMed)

Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y, Johnston SC; THALES Steering Committee and Investigators*. Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin. Stroke. 2020 Dec;51(12):3504-3513. doi: 10.1161/STROKEAHA.120.032239. Epub 2020 Nov 16.

Reference Type DERIVED
PMID: 33198608 (View on PubMed)

Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y, Johnston SC; THALES Steering Committee and Investigators. Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke: A Randomized Clinical Trial. JAMA Neurol. 2020 Nov 7;78(2):1-9. doi: 10.1001/jamaneurol.2020.4396. Online ahead of print.

Reference Type DERIVED
PMID: 33159526 (View on PubMed)

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y; THALES Investigators. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870.

Reference Type DERIVED
PMID: 32668111 (View on PubMed)

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y; THALES Investigators. The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) trial: Rationale and design. Int J Stroke. 2019 Oct;14(7):745-751. doi: 10.1177/1747493019830307. Epub 2019 Feb 12.

Reference Type DERIVED
PMID: 30747613 (View on PubMed)

Wong KSL, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Himmelmann A, Kasner SE, Knutsson M, Ladenvall P, Minematsu K, Molina CA, Wang Y, Johnston SC; SOCRATES Steering Committee and Investigators. Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial. Stroke. 2018 Jul;49(7):1678-1685. doi: 10.1161/STROKEAHA.118.020553. Epub 2018 Jun 18.

Reference Type DERIVED
PMID: 29915123 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

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Other Identifiers

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2016-004232-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5134C00003

Identifier Type: -

Identifier Source: org_study_id