EdoxabaN for IntraCranial Hemorrhage Survivors with Atrial Fibrillation (ENRICH-AF)

NCT ID: NCT03950076

Last Updated: 2025-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

948 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-20

Study Completion Date

2026-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation (ENRICH-AF) study is a prospective, randomized open-label, blinded end-point (PROBE), investigator-initiated, study that will define the efficacy and safety of edoxaban compared with non-anticoagulant medical therapy (no antithrombotic therapy or antiplatelet monotherapy) for stroke/systemic embolism prevention in high-risk AF patients and previous intracranial hemorrhage. Intracranial hemorrhage includes intracerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage and subdural hematoma. Recruitment will occur at 250-300 stroke research centres in North and South America, Europe and Asia over 24 months, where 1200 adult participants with high-risk AF (CHA2DS2-VASc score ≥2) and previous spontaneous or traumatic intracranial hemorrhage (while on or off antithrombotic therapy) will be randomly assigned to receive edoxaban 60/30 mg daily or to non-anticoagulant medical therapy (no antithrombotic therapy or antiplatelet monotherapy). Consenting participants will be followed to a common study end-date in this event-driven trial once 123 primary efficacy events (stroke) have accrued; anticipated to be about 12 months after the end of recruitment.

ENRICH-AF will assess the safety and efficacy of anticoagulant therapy in AF participants after intracranial hemorrhage, an area where there currently exists huge interest within the stroke and cardiology research communities. Demonstrating safety comparable with non-anticoagulant medical therapy in AF patients who are particularly at high risk for intracranial hemorrhage is likely to have a more far-reaching clinical impact than solely within the proposed study population. ENRICH-AF will be the "ultimate safety test" of anticoagulation of AF patients, providing reassuring evidence favoring more widespread use of anticoagulation for stroke prevention in AF patients.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Intracranial Hemorrhages Atrial Fibrillation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, randomized, open, blinded end-point (PROBE), multicenter international trial
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
open label study where outcomes assessor is blinded to treatment allocation

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Edoxaban 60/30mg daily

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

Group Type EXPERIMENTAL

Edoxaban

Intervention Type DRUG

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

Non-anticoagulant medical therapy

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

Group Type ACTIVE_COMPARATOR

Non-anticoagulant medical therapy

Intervention Type OTHER

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Edoxaban

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

Intervention Type DRUG

Non-anticoagulant medical therapy

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

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Lixiana Savaysa

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Written informed consent provided
2. Age ≥45 years, at the time of signing the informed consent
3. 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
4. Documented atrial fibrillation (paroxysmal, persistent, permanent)
5. CHA2DS2-VASc score ≥2

Exclusion Criteria

1. Recent intracranial hemorrhage (within 14 days)
2. Secondary macrovascular, neoplastic or infectious causes of intracranial hemorrhage (except for antithrombotic treatment or non-penetrating traumatic subdural hemorrhages)
3. 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
4. Need for ongoing oral anticoagulant therapy for indication other than AF (e.g. mechanical heart valve, venous thromboembolic disease)
5. Need for ongoing antiplatelet therapy for indication where edoxaban would not be a suitable substitute
6. Plans for left atrial appendage occlusion
7. Estimated creatinine clearance (CrCl) \< 15 mL/min
8. Platelet count less than 100,000mm3 at enrollment or other bleeding diathesis
9. Persistent, uncontrolled hypertension (systolic BP averaging \>150 mmHg)
10. Chronic use of NSAID
11. Clinically significant active bleeding, including gastrointestinal bleeding
12. 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
13. Antiphospholipid antibody syndrome
14. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
15. Known hypersensitivity to edoxaban
16. Estimated inability to adhere to study procedures
17. Pregnancy or breastfeeding
18. Estimated life expectancy \< 6 months at the time of enrollment
19. Close affiliation with the investigational site; e.g. a close relative for the investigator, dependent person (e.g., employee or student of the investigational site)
20. Lobar intraparenchymal hemorrhage

* Post menopausal female subjects must be amenorrheic for ≥12 months prior to screening or ≥6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) prior to screening. Women of childbearing potential must have negative serum pregnancy test within 7 days prior to randomization or urine pregnancy testing within 24 hours of randomization. Heterosexually active women of childbearing potential must use highly effective methods of contraception for 32 days after discontinuation (duration of study drug plus 30 days duration of one ovulatory cycle).
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Population Health Research Institute

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ashkan Shoamanesh, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Alexian Brothers Medical Center

Elk Grove Village, Illinois, United States

Site Status

Presence Care Transformation Corporation

Lisle, Illinois, United States

Site Status

Tulane University Medical Center

New Orleans, Louisiana, United States

Site Status

New York Presbyterian - Queens

Queens, New York, United States

Site Status

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

The University of Texas at Austin, Dell Medical School

Austin, Texas, United States

Site Status

Texas Tech University Health Sciences Center at El Paso

El Paso, Texas, United States

Site Status

Baylor St. Luke's Medical Center

Houston, Texas, United States

Site Status

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States

Site Status

Stat Research S.A.

Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Site Status

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

Buenos Aires, , Argentina

Site Status

Hospital Policial Churruca-Visca

Buenos Aires, , Argentina

Site Status

Centro Instituto Neurologico Salta

Salta, , Argentina

Site Status

Medical University of Innsbruck

Innsbruck, , Austria

Site Status

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

Rankweil, , Austria

Site Status

Medical University of Vienna, Dept. of Neurology

Vienna, , Austria

Site Status

Salzkammergutklinikum Vöcklabruck

Vöcklabruck, , Austria

Site Status

Erasme Hospital

Brussels, , Belgium

Site Status

UZ Brussel

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, , Belgium

Site Status

Ziekenhuis Oost-Limburg

Genk, , Belgium

Site Status

Jessa Hospital

Hasselt, , Belgium

Site Status

Groeninge Hospital

Kortrijk, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Clinique CHC MontLégia

Liège, , Belgium

Site Status

AZ Damiaan

Ostend, , Belgium

Site Status

AZ Delta

Roeselare, , Belgium

Site Status

Brandon Regional Health Centre

Brandon, , Canada

Site Status

University of Calgary / Foothills Medical Centre

Calgary, , Canada

Site Status

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

Chicoutimi, , Canada

Site Status

University of Alberta Hospital

Edmonton, , Canada

Site Status

Nova Scotia Health Authority

Halifax, , Canada

Site Status

Hamilton Health Sciences

Hamilton, , Canada

Site Status

Kingston General Hospital

Kingston, , Canada

Site Status

London Health Science Centre - University Hospital

London, , Canada

Site Status

CHUM Centre Hospitalier de l'Université de Montréal

Montreal, , Canada

Site Status

McGill University Health Centre

Montreal, , Canada

Site Status

The Ottawa Hospital Research Institute

Ottawa, , Canada

Site Status

The Rhema Research Institute

Owen Sound, , Canada

Site Status

CHUL Pavillon Enfant-Jésus

Québec, , Canada

Site Status

University of Saskatchewan

Saskatoon, , Canada

Site Status

Thunder Bay Regional Health Sciences Centre

Thunder Bay, , Canada

Site Status

Sunnybrook Health Science Centre

Toronto, , Canada

Site Status

University Health Network - Toronto Western Hospital

Toronto, , Canada

Site Status

Canadian Cardiac Research Centre

Windsor, , Canada

Site Status

Beijing Anzhen Hospital, Capital Medical University

Beijing, , China

Site Status

Punan Hospital

Shanghai, , China

Site Status

Shanghai Blue Cross Brain Hospital

Shanghai, , China

Site Status

Shanghai East Hospital, Tongji University

Shanghai, , China

Site Status

Shanghai Fengcheng Hospital

Shanghai, , China

Site Status

Xinhua Hospital, Chongming Branch

Shanghai, , China

Site Status

Yangpu Hospital, Tongji University

Shanghai, , China

Site Status

The First People's Hospital of Shenyang

Shenyang, , China

Site Status

St. Anne's University Hospital

Brno, , Czechia

Site Status

Neurological Department, General Hospital of Jihlava

Jihlava, , Czechia

Site Status

Cerebrovaskularni poradna s.r.o.

Ostrava, , Czechia

Site Status

Fayoum General Hospital

Al Fayyum, , Egypt

Site Status

Mansoura University Hospital

Al Mansurah, , Egypt

Site Status

Alexandria University Hospital

Alexandria, , Egypt

Site Status

Beni Suef University Hospital

Banī Suwayf, , Egypt

Site Status

Ain Shams Specialized Hospital

Cairo, , Egypt

Site Status

Ain Shams University Hospital

Cairo, , Egypt

Site Status

Tanta University Hospital

Tanta, , Egypt

Site Status

Zagazig University Hospital

Zagazig, , Egypt

Site Status

Charité - University Medicine Berlin

Berlin, , Germany

Site Status

Dresden University Hospital "Carl Gustav Carus"

Dresden, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Klinikum Friedrichshafen

Friedrichshafen, , Germany

Site Status

University Medicine Goettingen

Goettigen, , Germany

Site Status

Martha-Maria Hospital

Halle, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Klinikum Main-Spessart, Krankenhaus Lohr

Lohr, , Germany

Site Status

Klinik fur Neurologie, UKSH campus Lubeck

Lübeck, , Germany

Site Status

Medical Faculty Mannheim, Heidelberg University

Mannheim, , Germany

Site Status

Westfalische Wilhelms-Universitat Munster

Münster, , Germany

Site Status

Klinikum Osnabrück; Neurologie

Osnabrück, , Germany

Site Status

Department of Neurology, Klinikum Vest

Recklinghausen, , Germany

Site Status

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status

Zydus Hospitals & Healthcare Research Pvt. Ltd.

Ahmedabad, , India

Site Status

Shree Krishna Hospital and Pramukhswami Medical College

Anand, , India

Site Status

Bangalore Baptist Hospital

Bangalore, , India

Site Status

Fortis Hospital Ltd

Bangalore, , India

Site Status

Mazumdar Shaw Medical Center - Unit of Narayana Health

Bangalore, , India

Site Status

St. John's Medical College Hospital

Bangalore, , India

Site Status

Post Graduate Institute of Medical Education &Research

Chandigarh, , India

Site Status

Sikkim Manipal Institute of Medical Sciences

Gangtok, , India

Site Status

GNRC Hospitals

Guwahati, , India

Site Status

Bangur Institute of Neurosciences

Kolkata, , India

Site Status

Caritas Hospital

Kottayam, , India

Site Status

Christian Medical College & Hospital

Ludhiāna, , India

Site Status

Dhadiwal Hospital in coalition with Shreeji Healthcare

Nashik, , India

Site Status

Bharati Vidyapeeth (DTU) Medical College & Hospital

Pune, , India

Site Status

Nanjappa Hospital

Shimoga, , India

Site Status

Sree Chitra Tirunal Institute for Medical Sciences and Technology

Thiruvananthapuram, , India

Site Status

Rhythm Heart Institute

Vadodara, , India

Site Status

Chitwan Everest Asptalal Private limited

Bharatpur, , Nepal

Site Status

Chitwan Medical College Teaching Hospital

Bharatpur, , Nepal

Site Status

Nobel Medical College & Teaching Hospital

Biratnagar, , Nepal

Site Status

B P Koirala Institute of Health Sciences

Dharān, , Nepal

Site Status

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

Jhapa, , Nepal

Site Status

Annapurna Neurological institute and allied sciences

Kathmandu, , Nepal

Site Status

Grande International Hospital

Kathmandu, , Nepal

Site Status

Kathmandu Medical College

Kathmandu, , Nepal

Site Status

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

Kathmandu, , Nepal

Site Status

CHULN-Hospital Santa Maria

Lisbon, , Portugal

Site Status

Coruña University Hospital

A Coruña, , Spain

Site Status

University Hospital of Albacete

Albacete, , Spain

Site Status

Instituto de Investigacion Sanitaria Biocruces

Barakaldo, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital de La Santa Creu Isant Pau

Barcelona, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Complejo Hospitalario Universitario de Cáceres

Cáceres, , Spain

Site Status

Hospital Donostia - Osidonostialdea

Donostia / San Sebastian, , Spain

Site Status

Hospital u Arnau de Vilanova de Lleida

Lleida, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Ramón y Cajal

Madrid, , Spain

Site Status

La Paz Univerity Hospital

Madrid, , Spain

Site Status

Hospital Universitario Central de Asturias-Finba

Oviedo, , Spain

Site Status

Hospital Universitario son Espases

Palma de Mallorca, , Spain

Site Status

Hospital Universitari i Politécnic La Fe.

Valencia, , Spain

Site Status

University Hospital Basel

Basel, , Switzerland

Site Status

Inselspital, University Hospital Bern

Bern, , Switzerland

Site Status

Aberdeen Royal Infirmary, NHS Grampian

Aberdeen, , United Kingdom

Site Status

Nevill Hall Hospital

Abergavenny, , United Kingdom

Site Status

NHS Lanarkshire Health Board - Monklands Hospital

Airdrie, , United Kingdom

Site Status

Arrowe Park Hospital

Birkenhead, , United Kingdom

Site Status

The Royal Bournemouth Hospital

Bournemouth, , United Kingdom

Site Status

Bradford Teaching Hospitals NHS Foundation Trust, at Bradford Royal Infirmary

Bradford, , United Kingdom

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

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

Colchester, , United Kingdom

Site Status

Edinburgh Royal Infirmary

Edinburgh, , United Kingdom

Site Status

Queen Elizabeth Hospital - Gateshead Health NHS Foundation Trust

Gateshead, , United Kingdom

Site Status

Glasgow Royal Infirmary

Glasgow, , United Kingdom

Site Status

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, , United Kingdom

Site Status

LNWUH - Northwick Park Hospital

Harrow, , United Kingdom

Site Status

Calderdale and Huddersfield NHS Foundation Trust

Huddersfield, , United Kingdom

Site Status

Victoria Hospital Kirkcaldy

Kirkcaldy, , United Kingdom

Site Status

Homerton University Hospital

London, , United Kingdom

Site Status

King's Mill Hospital

Mansfield, , United Kingdom

Site Status

The South Tees Hospitals NHS Foundation Trust

Middlesbrough, , United Kingdom

Site Status

Morriston Hospital

Morriston, , United Kingdom

Site Status

Royal Preston Hospital

Preston, , United Kingdom

Site Status

Royal Berkshire NHS Foundation Trust

Reading, , United Kingdom

Site Status

Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Hillingdon Hospital

Uxbridge, , United Kingdom

Site Status

Southend University Hospital Southend University Hospital NHS Foundation Trust

Westcliff-on-Sea, , United Kingdom

Site Status

Yeovil District Hospital

Yeovil, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Austria Belgium Canada China Czechia Egypt Germany India Nepal Portugal Spain Switzerland United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 36700520 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34022170 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ENRICH-AF

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Edoxaban for TIA and Acute Minor Stroke
NCT02221102 UNKNOWN PHASE2/PHASE3