NCT03950076

Brief Summary

To assess whether edoxaban (60/30 mg daily) compared to non-antithrombotic medical therapy (either no antithrombotic therapy or antiplatelet monotherapy) reduces the risk of stroke (composite of ischemic, hemorrhagic and unspecified stroke) or systemic embolism in high-risk atrial fibrillation (CHA2DS2-VASc ≥2) patients with previous intracranial hemorrhage.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
948

participants targeted

Target at P75+ for phase_4

Timeline
0mo left

Started Sep 2019

Longer than P75 for phase_4

Geographic Reach
15 countries

152 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 10, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 15, 2019

Completed
4 months until next milestone

Study Start

First participant enrolled

September 20, 2019

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 13, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 13, 2026

Last Updated

February 25, 2026

Status Verified

February 1, 2026

Enrollment Period

6.6 years

First QC Date

May 10, 2019

Last Update Submit

February 23, 2026

Conditions

Keywords

EdoxabanIntracranial HemorrhageHemorrhagic Stroke

Outcome Measures

Primary Outcomes (2)

  • Stroke or Systemic Embolism

    Stroke (composite of ischemic, hemorrhagic and unspecified) or systemic embolism

    From randomization until the common study end date (average of 3 years)

  • Major hemorrhage

    as defined byt the International Society on Thrombosis and Haemostasis (ISTH) criteria

    From randomization until the common study end date (median 2 years)

Secondary Outcomes (11)

  • Ischemic stroke

    From randomization until the common study end date (median 2 years)

  • Cardiovascular death

    From randomization until the common study end date (median 2 years)

  • Hemorrhagic stroke

    From randomization until the common study end date (median 2 years)

  • Disabling/fatal stroke

    From randomization until the common study end date (median 2 years)

  • Composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death

    From randomization until the common study end date (median 2 years)

  • +6 more secondary outcomes

Study Arms (2)

Edoxaban 60/30mg daily

EXPERIMENTAL

Edoxaban 60/30 mg daily (lower dose depending on clinical criteria)

Drug: Edoxaban

Non-anticoagulant medical therapy

ACTIVE COMPARATOR

Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator)

Other: Non-anticoagulant medical therapy

Interventions

Edoxaban 60mg (or 30mg as determined by clinical criteria)

Also known as: Lixiana, Savaysa
Edoxaban 60/30mg daily

Non-anticoagulant medical therapy as determined by the local investigator includes i) No antithrombotic therapy ii) Antiplatelet monotherapy, including de novo indication for antiplatelet monotherapy during course of the study

Non-anticoagulant medical therapy

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent provided
  • Age ≥45 years, at the time of signing the informed consent
  • Previous intracranial hemorrhage (symptomatic, spontaneous and non-traumatic non-lobar intraparenchymal or intraventricular hemorrhage, and symptomatic spontaneous or non-penetrating traumatic subdural hemorrhages) on or off antithrombotic therapy
  • Documented atrial fibrillation (paroxysmal, persistent, permanent)
  • CHA2DS2-VASc score ≥2

You may not qualify if:

  • Recent intracranial hemorrhage (within 14 days)
  • Secondary macrovascular, neoplastic or infectious causes of intracranial hemorrhage (except for antithrombotic treatment or non-penetrating traumatic subdural hemorrhages)
  • Isolated subarachnoid hemorrhage (convexity or basal); subarachnoid blood tracking onto convexity secondary to an intraventricular hemorrhage or as part of a multicompartment bleed in cases of traumatic subdural hemorrhages are eligible
  • Need for ongoing oral anticoagulant therapy for indication other than AF (e.g. mechanical heart valve, venous thromboembolic disease)
  • Need for ongoing antiplatelet therapy for indication where edoxaban would not be a suitable substitute
  • Plans for left atrial appendage occlusion
  • Estimated creatinine clearance (CrCl) \< 15 mL/min
  • Platelet count less than 100,000mm3 at enrollment or other bleeding diathesis
  • Persistent, uncontrolled hypertension (systolic BP averaging \>150 mmHg)
  • Chronic use of NSAID
  • Clinically significant active bleeding, including gastrointestinal bleeding
  • Lesions or conditions at increased risk of clinically significant bleeding, e.g. active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis
  • Antiphospholipid antibody syndrome
  • Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
  • Known hypersensitivity to edoxaban
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (152)

Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

Presence Care Transformation Corporation

Lisle, Illinois, 60532, United States

Location

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

New York Presbyterian - Queens

Queens, New York, 11355, United States

Location

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15218, United States

Location

The University of Texas at Austin, Dell Medical School

Austin, Texas, 78701, United States

Location

Texas Tech University Health Sciences Center at El Paso

El Paso, Texas, 79905, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

MultiCare Institute for Research & Innovation

Tacoma, Washington, 98405, United States

Location

Stat Research S.A.

Buenos Aires, C1023AAB, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199 CABA, Argentina

Location

Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI)

Buenos Aires, C1428 CABA, Argentina

Location

Hospital Policial Churruca-Visca

Buenos Aires, C1437 JCP, Argentina

Location

Centro Instituto Neurologico Salta

Salta, Argentina

Location

Medical University of Innsbruck

Innsbruck, Austria

Location

Institut für Akutneurologie und Stroke Unit (IANS), Landeskrankenhaus Feldkirch

Rankweil, Austria

Location

Medical University of Vienna, Dept. of Neurology

Vienna, Austria

Location

Salzkammergutklinikum Vöcklabruck

Vöcklabruck, Austria

Location

Erasme Hospital

Brussels, Belgium

Location

UZ Brussel

Brussels, Belgium

Location

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, Belgium

Location

Jessa Hospital

Hasselt, Belgium

Location

Groeninge Hospital

Kortrijk, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Clinique CHC MontLégia

Liège, Belgium

Location

AZ Damiaan

Ostend, Belgium

Location

AZ Delta

Roeselare, Belgium

Location

Brandon Regional Health Centre

Brandon, Canada

Location

University of Calgary / Foothills Medical Centre

Calgary, Canada

Location

Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay-Lac-Saint-Jean

Chicoutimi, Canada

Location

University of Alberta Hospital

Edmonton, Canada

Location

Nova Scotia Health Authority

Halifax, Canada

Location

Hamilton Health Sciences

Hamilton, Canada

Location

Kingston General Hospital

Kingston, Canada

Location

London Health Science Centre - University Hospital

London, Canada

Location

CHUM Centre Hospitalier de l'Université de Montréal

Montreal, Canada

Location

McGill University Health Centre

Montreal, Canada

Location

The Ottawa Hospital Research Institute

Ottawa, Canada

Location

The Rhema Research Institute

Owen Sound, Canada

Location

CHUL Pavillon Enfant-Jésus

Québec, Canada

Location

University of Saskatchewan

Saskatoon, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Canada

Location

Sunnybrook Health Science Centre

Toronto, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Canada

Location

Canadian Cardiac Research Centre

Windsor, Canada

Location

Beijing Anzhen Hospital, Capital Medical University

Beijing, China

Location

Punan Hospital

Shanghai, China

Location

Shanghai Blue Cross Brain Hospital

Shanghai, China

Location

Shanghai East Hospital, Tongji University

Shanghai, China

Location

Shanghai Fengcheng Hospital

Shanghai, China

Location

Xinhua Hospital, Chongming Branch

Shanghai, China

Location

Yangpu Hospital, Tongji University

Shanghai, China

Location

The First People's Hospital of Shenyang

Shenyang, China

Location

St. Anne's University Hospital

Brno, Czechia

Location

Neurological Department, General Hospital of Jihlava

Jihlava, Czechia

Location

Cerebrovaskularni poradna s.r.o.

Ostrava, Czechia

Location

Fayoum General Hospital

Al Fayyum, Egypt

Location

Mansoura University Hospital

Al Mansurah, Egypt

Location

Alexandria University Hospital

Alexandria, Egypt

Location

Beni Suef University Hospital

Banī Suwayf, Egypt

Location

Ain Shams Specialized Hospital

Cairo, Egypt

Location

Ain Shams University Hospital

Cairo, Egypt

Location

Tanta University Hospital

Tanta, Egypt

Location

Zagazig University Hospital

Zagazig, Egypt

Location

Charité - University Medicine Berlin

Berlin, Germany

Location

Dresden University Hospital "Carl Gustav Carus"

Dresden, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Klinikum Friedrichshafen

Friedrichshafen, Germany

Location

University Medicine Goettingen

Goettigen, Germany

Location

Martha-Maria Hospital

Halle, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Klinikum Main-Spessart, Krankenhaus Lohr

Lohr, Germany

Location

Klinik fur Neurologie, UKSH campus Lubeck

Lübeck, Germany

Location

Medical Faculty Mannheim, Heidelberg University

Mannheim, Germany

Location

Westfalische Wilhelms-Universitat Munster

Münster, Germany

Location

Klinikum Osnabrück; Neurologie

Osnabrück, Germany

Location

Department of Neurology, Klinikum Vest

Recklinghausen, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Zydus Hospitals & Healthcare Research Pvt. Ltd.

Ahmedabad, India

Location

Shree Krishna Hospital and Pramukhswami Medical College

Anand, India

Location

Bangalore Baptist Hospital

Bangalore, India

Location

Fortis Hospital Ltd

Bangalore, India

Location

Mazumdar Shaw Medical Center - Unit of Narayana Health

Bangalore, India

Location

St. John's Medical College Hospital

Bangalore, India

Location

Post Graduate Institute of Medical Education &Research

Chandigarh, India

Location

Sikkim Manipal Institute of Medical Sciences

Gangtok, India

Location

GNRC Hospitals

Guwahati, India

Location

Bangur Institute of Neurosciences

Kolkata, India

Location

Caritas Hospital

Kottayam, India

Location

Christian Medical College & Hospital

Ludhiāna, India

Location

Dhadiwal Hospital in coalition with Shreeji Healthcare

Nashik, India

Location

Bharati Vidyapeeth (DTU) Medical College & Hospital

Pune, India

Location

Nanjappa Hospital

Shimoga, India

Location

Sree Chitra Tirunal Institute for Medical Sciences and Technology

Thiruvananthapuram, India

Location

Rhythm Heart Institute

Vadodara, India

Location

Chitwan Everest Asptalal Private limited

Bharatpur, Nepal

Location

Chitwan Medical College Teaching Hospital

Bharatpur, Nepal

Location

Nobel Medical College & Teaching Hospital

Biratnagar, Nepal

Location

B P Koirala Institute of Health Sciences

Dharān, Nepal

Location

B & C Medical College Teaching Hospital & Research Centre Pvt. Ltd.

Jhapa, Nepal

Location

Annapurna Neurological institute and allied sciences

Kathmandu, Nepal

Location

Grande International Hospital

Kathmandu, Nepal

Location

Kathmandu Medical College

Kathmandu, Nepal

Location

Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences (UDMNINAS)

Kathmandu, Nepal

Location

CHULN-Hospital Santa Maria

Lisbon, Portugal

Location

Coruña University Hospital

A Coruña, Spain

Location

University Hospital of Albacete

Albacete, Spain

Location

Instituto de Investigacion Sanitaria Biocruces

Barakaldo, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital de La Santa Creu Isant Pau

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Complejo Hospitalario Universitario de Cáceres

Cáceres, Spain

Location

Hospital Donostia - Osidonostialdea

Donostia / San Sebastian, Spain

Location

Hospital u Arnau de Vilanova de Lleida

Lleida, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

La Paz Univerity Hospital

Madrid, Spain

Location

Hospital Universitario Central de Asturias-Finba

Oviedo, Spain

Location

Hospital Universitario son Espases

Palma de Mallorca, Spain

Location

Hospital Universitari i Politécnic La Fe.

Valencia, Spain

Location

University Hospital Basel

Basel, Switzerland

Location

Inselspital, University Hospital Bern

Bern, Switzerland

Location

Aberdeen Royal Infirmary, NHS Grampian

Aberdeen, United Kingdom

Location

Nevill Hall Hospital

Abergavenny, United Kingdom

Location

NHS Lanarkshire Health Board - Monklands Hospital

Airdrie, United Kingdom

Location

Arrowe Park Hospital

Birkenhead, United Kingdom

Location

The Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Bradford Teaching Hospitals NHS Foundation Trust, at Bradford Royal Infirmary

Bradford, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

East Suffolk and North Essex NHS Foundation Trust, at Colchester Hospital

Colchester, United Kingdom

Location

Edinburgh Royal Infirmary

Edinburgh, United Kingdom

Location

Queen Elizabeth Hospital - Gateshead Health NHS Foundation Trust

Gateshead, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Gloucestershire Royal Hospital

Gloucester, United Kingdom

Location

LNWUH - Northwick Park Hospital

Harrow, United Kingdom

Location

Calderdale and Huddersfield NHS Foundation Trust

Huddersfield, United Kingdom

Location

Victoria Hospital Kirkcaldy

Kirkcaldy, United Kingdom

Location

Homerton University Hospital

London, United Kingdom

Location

King's Mill Hospital

Mansfield, United Kingdom

Location

The South Tees Hospitals NHS Foundation Trust

Middlesbrough, United Kingdom

Location

Morriston Hospital

Morriston, United Kingdom

Location

Royal Preston Hospital

Preston, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Hillingdon Hospital

Uxbridge, United Kingdom

Location

Southend University Hospital Southend University Hospital NHS Foundation Trust

Westcliff-on-Sea, United Kingdom

Location

Yeovil District Hospital

Yeovil, United Kingdom

Location

Related Publications (2)

  • Cochrane A, Chen C, Stephen J, Ronning OM, Anderson CS, Hankey GJ, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD012144. doi: 10.1002/14651858.CD012144.pub3.

  • Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2.

MeSH Terms

Conditions

Intracranial HemorrhagesAtrial FibrillationHemorrhagic Stroke

Interventions

edoxaban

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and SymptomsArrhythmias, CardiacHeart DiseasesStroke

Study Officials

  • Ashkan Shoamanesh, MD, FRCPC

    Population Health Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
open label study where outcomes assessor is blinded to treatment allocation
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Prospective, randomized, open, blinded end-point (PROBE), multicenter international trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 10, 2019

First Posted

May 15, 2019

Study Start

September 20, 2019

Primary Completion (Estimated)

May 13, 2026

Study Completion (Estimated)

May 13, 2026

Last Updated

February 25, 2026

Record last verified: 2026-02

Locations