Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03950076
Other study ID # ENRICH-AF
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date September 20, 2019
Est. completion date October 2024

Study information

Verified date February 2024
Source Population Health Research Institute
Contact Kevin Reeh, MSc
Phone 905-521-2100
Email ENRICH-AF@phri.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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) in high-risk atrial fibrillation (CHA2DS2-VASc ≥2) patients with previous intracranial hemorrhage.


Description:

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 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 1200
Est. completion date October 2024
Est. primary completion date October 2024
Accepts healthy volunteers No
Gender All
Age group 45 Years and older
Eligibility 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).

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Argentina Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) Buenos Aires
Argentina Hospital Italiano de Buenos Aires Buenos Aires
Argentina Hospital Policial Churruca-Visca Buenos Aires
Argentina Stat Research S.A. Buenos Aires
Argentina Centro Instituto Neurologico Salta Salta
Austria Medical University of Innsbruck Innsbruck
Austria Institut für Akutneurologie und Stroke Unit (IANS), Landeskrankenhaus Feldkirch Rankweil
Austria Medical University of Vienna, Dept. of Neurology Vienna
Austria Salzkammergutklinikum Vöcklabruck Vocklabruck
Belgium Erasme Hospital Brussel
Belgium UZ Brussel Brussel
Belgium Universitair Ziekenhuis Antwerpen (UZA) Edegem
Belgium Ziekenhuis Oost-Limburg Genk
Belgium Jessa Hospital Hasselt
Belgium Groeninge Hospital Kortrijk
Belgium UZ Leuven Leuven
Belgium Clinique CHC MontLégia Liège
Belgium AZ Damiaan Oostende
Belgium AZ Delta Roeselare
Canada Brandon Regional Health Centre Brandon
Canada University of Calgary / Foothills Medical Centre Calgary
Canada Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay-Lac-Saint-Jean Chicoutimi
Canada University of Alberta Hospital Edmonton
Canada Nova Scotia Health Authority Halifax
Canada Hamilton Health Sciences Hamilton
Canada Hamilton Health Sciences Hamilton
Canada Kingston General Hospital Kingston
Canada London Health Science Centre - University Hospital London
Canada CHUM Centre Hospitalier de l'Université de Montréal Montreal
Canada McGill University Health Centre Montréal
Canada The Ottawa Hospital Research Institute Ottawa
Canada The Rhema Research Institute Owen Sound
Canada CHUL Pavillon Enfant-Jésus Québec
Canada University of Saskatchewan Saskatoon
Canada Thunder Bay Regional Health Sciences Centre Thunder Bay
Canada Sunnybrook Health Science Centre Toronto
Canada University Health Network - Toronto Western Hospital Toronto
Canada Canadian Cardiac Research Centre Windsor
China Beijing Anzhen Hospital, Capital Medical University Beijing
China Punan Hospital Shanghai
China Shanghai Blue Cross Brain Hospital Shanghai
China Shanghai East Hospital, Tongji University Shanghai
China Shanghai Fengcheng Hospital Shanghai
China Xinhua Hospital, Chongming Branch Shanghai
China Yangpu Hospital, Tongji University Shanghai
China The First People's Hospital of Shenyang Shenyang
Czechia St. Anne's University Hospital Brno
Czechia Neurological Department, General Hospital of Jihlava Jihlava
Czechia Cerebrovaskularni poradna s.r.o. Ostrava
Egypt Alexandria University Hospital Alexandria
Egypt Beni Suef University Hospital Bani Suwayf
Egypt Ain Shams Specialized Hospital Cairo
Egypt Ain Shams University Hospital Cairo
Egypt Fayoum General Hospital Fayoum
Egypt Mansoura University Hospital Mansoura
Egypt Tanta University Hospital Tanta
Egypt Zagazig University Hospital Zagazig
Germany Charité - University Medicine Berlin Berlin
Germany Dresden University Hospital "Carl Gustav Carus" Dresden
Germany Universitätsklinikum Essen Essen
Germany Klinikum Friedrichshafen Friedrichshafen
Germany University Medicine Goettingen Goettigen
Germany Martha-Maria Hospital Halle
Germany Universitätsklinikum Hamburg-Eppendorf Hamburg
Germany Klinikum Main-Spessart, Krankenhaus Lohr Lohr
Germany Klinik fur Neurologie, UKSH campus Lubeck Lübeck
Germany Medical Faculty Mannheim, Heidelberg University Mannheim
Germany Westfalische Wilhelms-Universitat Munster Münster
Germany Klinikum Osnabrück; Neurologie Osnabrück
Germany Department of Neurology, Klinikum Vest Recklinghausen
Germany Universitätsklinikum Tübingen Tuebingen
India Zydus Hospitals & Healthcare Research Pvt. Ltd. Ahmedabad
India Shree Krishna Hospital and Pramukhswami Medical College Anand
India Bangalore Baptist Hospital Bangalore
India Fortis Hospital Ltd Bangalore
India Mazumdar Shaw Medical Center - Unit of Narayana Health Bangalore
India St. John's Medical College Hospital Bangalore
India Post Graduate Institute of Medical Education &Research Chandigarh
India Sikkim Manipal Institute of Medical Sciences Gangtok
India GNRC Hospitals Guwahati
India Bangur Institute of Neurosciences Kolkata
India Caritas Hospital Kottayam
India Christian Medical College & Hospital Ludhiana
India Dhadiwal Hospital in coalition with Shreeji Healthcare Nashik
India Bharati Vidyapeeth (DTU) Medical College & Hospital Pune
India Nanjappa Hospital Shimoga
India Sree Chitra Tirunal Institute for Medical Sciences and Technology Thiruvananthapuram
India Rhythm Heart Institute Vadodara
Nepal Chitwan Everest Asptalal Private limited Bharatpur
Nepal Chitwan Medical College Teaching Hospital Bharatpur
Nepal Nobel Medical College & Teaching Hospital Biratnagar
Nepal B P Koirala Institute of Health Sciences Dharan Bazar
Nepal B & C Medical College Teaching Hospital & Research Centre Pvt. Ltd. Jhapa
Nepal Annapurna Neurological institute and allied sciences Kathmandu
Nepal Grande International Hospital Kathmandu
Nepal Kathmandu Medical College Kathmandu
Nepal Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences (UDMNINAS) Kathmandu
Portugal CHULN-Hospital Santa Maria Lisboa
Spain Coruña University Hospital A Coruña
Spain University Hospital of Albacete Albacete
Spain Instituto de Investigacion Sanitaria Biocruces Barakaldo
Spain Hospital Clinic de Barcelona Barcelona
Spain Hospital de La Santa Creu Isant Pau Barcelona
Spain Hospital del Mar Barcelona
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Complejo Hospitalario Universitario de Cáceres Cáceres
Spain Hospital Donostia - Osidonostialdea Donostia
Spain Hospital u Arnau de Vilanova de Lleida Lleida
Spain Hospital General Universitario Gregorio Marañon Madrid
Spain Hospital Ramón y Cajal Madrid
Spain La Paz Univerity Hospital Madrid
Spain Hospital Universitario Central de Asturias-Finba Oviedo
Spain Hospital Universitario son Espases Palma De Mallorca
Spain Hospital Universitari i Politécnic La Fe. Valencia
Switzerland University Hospital Basel Basel
Switzerland Inselspital, University Hospital Bern Bern
United Kingdom Aberdeen Royal Infirmary, NHS Grampian Aberdeen
United Kingdom Nevill Hall Hospital Abergavenny
United Kingdom NHS Lanarkshire Health Board - Monklands Hospital Airdrie
United Kingdom Arrowe Park Hospital Birkenhead
United Kingdom The Royal Bournemouth Hospital Bournemouth
United Kingdom Bradford Teaching Hospitals NHS Foundation Trust, at Bradford Royal Infirmary Bradford
United Kingdom Cambridge University Hospitals NHS Foundation Trust Cambridge
United Kingdom University Hospital of Wales Cardiff
United Kingdom East Suffolk and North Essex NHS Foundation Trust, at Colchester Hospital Colchester
United Kingdom Edinburgh Royal Infirmary Edinburgh
United Kingdom Queen Elizabeth Hospital - Gateshead Health NHS Foundation Trust Gateshead
United Kingdom Glasgow Royal Infirmary Glasgow
United Kingdom Queen Elizabeth University Hospital Glasgow
United Kingdom Gloucestershire Royal Hospital Gloucester
United Kingdom LNWUH - Northwick Park Hospital Harrow
United Kingdom Calderdale and Huddersfield NHS Foundation Trust Huddersfield
United Kingdom Victoria Hospital Kirkcaldy Kirkcaldy
United Kingdom Homerton University Hospital London
United Kingdom King's Mill Hospital Mansfield
United Kingdom The South Tees Hospitals NHS Foundation Trust Middlesbrough
United Kingdom Morriston Hospital Morriston
United Kingdom Royal Preston Hospital Preston
United Kingdom Royal Berkshire NHS Foundation Trust Reading
United Kingdom Royal Cornwall Hospital Truro
United Kingdom Hillingdon Hospital Uxbridge
United Kingdom Southend University Hospital Southend University Hospital NHS Foundation Trust Westcliff-on-Sea
United Kingdom Yeovil District Hospital Yeovil
United States The University of Texas at Austin, Dell Medical School Austin Texas
United States Texas Tech University Health Sciences Center at El Paso El Paso Texas
United States Alexian Brothers Medical Center Elk Grove Village Illinois
United States Baylor St. Luke's Medical Center Houston Texas
United States Presence Care Transformation Corporation Lisle Illinois
United States Tulane University Medical Center New Orleans Louisiana
United States The Hospital of the University of Pennsylvania Philadelphia Pennsylvania
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States New York Presbyterian - Queens Queens New York
United States MultiCare Institute for Research & Innovation Tacoma Washington

Sponsors (1)

Lead Sponsor Collaborator
Population Health Research Institute

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Stroke composite of ischemic, hemorrhagic and unspecified From randomization until the common study end date (median 2 years)
Primary 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 Ischemic stroke development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke. From randomization until the common study end date (median 2 years)
Secondary Cardiovascular death Death related to cardiovascular cause From randomization until the common study end date (median 2 years)
Secondary Hemorrhagic stroke development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute intraparenchymal, intraventricular or subarachnoid hemorrhage From randomization until the common study end date (median 2 years)
Secondary Disabling/fatal stroke Disabling stroke is defined as stroke resulting in a clinical outcome that is associated with a modified Rankin scale of 4 or 5. Fatal stroke is defined as death occurring within 30 days of stroke. From randomization until the common study end date (median 2 years)
Secondary Composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death Components of composite outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging),myocardial infarction, systemic thromboembolism or all-cause death. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred From randomization until the common study end date (median 2 years)
Secondary Net clinical benefit (composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area) Net clinical benefit is a composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area From randomization until the common study end date (median 2 years)
Secondary modified Rankin Scale mRS as measured at 12 month visit 12 months
Secondary All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage) Intracranial hemorrhage as defined by Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy. From randomization until the common study end date (median 2 years)
Secondary Fatal intracranial hemorrhage Inctracranial hemorrhage defined as Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy with death occurring within 30 days of stroke From randomization until the common study end date (median 2 years)
Secondary Subdural hemorrhage Subdural hemorrhage as defined as Signs or symptoms associated with a subdural hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy From randomization until the common study end date (median 2 years)
Secondary Hospitalization for any cause Minimum of one overnight stay in hospital. From randomization until the common study end date (median 2 years)
See also
  Status Clinical Trial Phase
Recruiting NCT05654272 - Development of CIRC Technologies
Completed NCT04571385 - A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) Phase 2
Terminated NCT04115735 - His Bundle Recording From Subclavian Vein
Completed NCT05366803 - Women's Health Initiative Silent Atrial Fibrillation Recording Study N/A
Completed NCT02864758 - Benefit-Risk Of Arterial THrombotic prEvention With Rivaroxaban for Atrial Fibrillation in France
Recruiting NCT05442203 - Electrocardiogram-based Artificial Intelligence-assisted Detection of Heart Disease N/A
Completed NCT05599308 - Evaluation of Blood Pressure Monitor With AFib Screening Feature N/A
Completed NCT03790917 - Assessment of Adherence to New Oral anTicoagulants in Atrial Fibrillation patiEnts Within the Outpatient registrY
Enrolling by invitation NCT05890274 - Atrial Fibrillation (AF) and Electrocardiogram (EKG) Interpretation Project ECHO N/A
Recruiting NCT05316870 - Construction and Effect Evaluation of Anticoagulation Management Model in Atrial Fibrillation N/A
Recruiting NCT05266144 - Atrial Fibrillation Patients Treated With Catheter Ablation
Not yet recruiting NCT06023784 - The Impact of LBBAP vs RVP on the Incidence of New-onset Atrial Fibrillation in Patients With Atrioventricular Block N/A
Recruiting NCT05572814 - Transform: Teaching, Technology, and Teams N/A
Recruiting NCT04092985 - Smart Watch iECG for the Detection of Cardiac Arrhythmias
Completed NCT04087122 - Evaluate the Efficiency Impact of Conducting Active Temperature Management During Cardiac Cryoablation Procedures N/A
Completed NCT06283654 - Relieving the Emergency Department by Using a 1-lead ECG Device for Atrial Fibrillation Patients After Pulmonary Vein Isolation
Recruiting NCT05416086 - iCLAS™ Cryoablation System Post-Market Clinical Follow-up (PMCF) Study N/A
Completed NCT05067114 - Solutions for Atrial Fibrillation Edvocacy (SAFE)
Completed NCT04546763 - Study Watch AF Detection At Home
Completed NCT03761394 - Pulsewatch: Smartwatch Monitoring for Atrial Fibrillation After Stroke N/A