EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hamilton Health Sciences Corporation, PHRI Population Health Research Institute International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-12-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, United States

External identifiers

EU CT number

2024-518508-31-00

EudraCT number

2019-002075-33

ClinicalTrials.gov

NCT03950076

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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

Secondary objectives 2

1. i) To assess whether edoxaban (60/30 mg daily) compared to non- anticoagulant medical therapy (either no antithrombotic therapy or antiplatelet monotherapy) reduces the risk of cardiovascular death in high-risk atrial fibrillation participants with previous intracranial hemorrhage.
2. ii) To assess whether edoxaban (60/30 mg daily) is associated with increased risk of major hemorrhage compared to standard of care (either no antithrombotic therapy or antiplatelet monotherapy).

Conditions and MedDRA coding

High risk atrial fibrillation patients with previous intracranial hemorrhage

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 21

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 or other creatinine clearance following local product monograph (Canada < 30mL/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 hemorrhages
21. * 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary efficacy end point is composite risk of stroke (ischemic, hemorrhagic and unspecified stroke) or systemic embolism.
2. The primary safety endpoint is major hemorrhage as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria

Secondary endpoints 12

1. Ischemic stroke
2. Cardiovascular death
3. Hemorrhagic stroke
4. Disabling/fatal stroke
5. Systemic embolism
6. Composite of all stroke, myocardial infarction, systemic embolism or all cause death
7. Net clinical benefit (composite of stroke, systemic embolism, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area)
8. Modified Rankin scale (mRS) at 12 months
9. The secondary safety end point(s) are: All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage)
10. Fatal intracranial hemorrhage
11. Subdural hemorrhage
12. Hospitalization for any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hamilton Health Sciences Corporation

Sponsor organisation

Hamilton Health Sciences Corporation

Address

100 King Street West

City

Hamilton

Postcode

L8P 1A2

Country

Canada

Scientific contact point

Organisation

Hamilton Health Sciences Corporation

Contact name

Dr. Ashkan Shoamanesh

Public contact point

Organisation

Hamilton Health Sciences Corporation

Contact name

ENRICH-AF Project Office

PHRI Population Health Research Institute International

Sponsor organisation

PHRI Population Health Research Institute International

Address

237 Barton Street East

City

Hamilton

Postcode

L8L 2X2

Country

Canada

Scientific contact point

Organisation

PHRI Population Health Research Institute International

Contact name

Dr. Ashkan Shoamanesh

Public contact point

Organisation

PHRI Population Health Research Institute International

Contact name

ENRICH-AF Research Project Office

Third parties 2

Locations

10 EU/EEA countries · 65 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 119 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications