Home » Trials » SLCTR/2022/005


EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation

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SLCTR Registration Number

SLCTR/2022/005


Date of Registration

30 Mar 2022

The date of last modification

Mar 30, 2022



Application Summary


Scientific Title of Trial

EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation


Public Title of Trial

Prospective, randomized, open-label, blinded end-point (PROBE), multicenter international trial 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 stroke in high-risk atrial fibrillation patients with previous intracranial hemorrhage


Disease or Health Condition(s) Studied

Intracranial Hemorrhages, Atrial Fibrillation


Scientific Acronym

ENRICH-AF


Public Acronym

ENRICH-AF


Brief title

None


Universal Trial Number

U1111-1271-7894


Any other number(s) assigned to the trial and issuing authority

NCT03950076 (ClinicalTrials.gov)


Trial Details


What is the research question being addressed?

What is 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 haemorrhage?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Single blinded : Outcome assessors


Control

Standard therapy/practice


Assignment

Parallel


Purpose

Prevention


Study Phase

Phase 4


Intervention(s) planned

Study Sites •National Hospital of Sri Lanka •Colombo South Teaching Hospital •Kurunegala Teaching Hospital •Karapitiya Teaching Hospital •Sri Jayewardenepura General Hospital •Negombo District General Hospital •National Hospital, Kandy

Participants who satisfy the eligibility criteria and complete protocol related activities relevant to screening visit will be randomly allocated in a 1:1 ratio to open label intervention edoxaban [60/30 mg daily] or non-anticoagulant medical therapy (either no antithrombotic therapy or antiplatelet monotherapy). Randomization will occur any time after 14 days since the time of the qualifying intracranial hemorrhage. Exact timing will be left to the discretion and equipoise of the local investigator.

The administration of the 60mg daily or 30mg daily will be determined by the following criteria. Dose will be 60 mg unless any of the following conditions are met in which case the dose will be 30mg.

1.Estimated Creatinine-clearance 15-49 mL/min 2.body weight greater or equal to 60 kg 3.Concomitant use of potent P-glycoprotein inhibitors (a country specific dosing guidance document will be provided).

Participants who are allocated to the open label intervention Edoxaban arm will be receiving tablet 30 mg or 60 mg once daily. For participants randomly assigned to receive non-anticoagulant medical therapy, the local site investigator will determine treatment, which may or may not include antiplatelet monotherapy but will not include oral anticoagulation or left atrial appendage occlusion.

Participants will be followed every 6 months until the common study end date. This study is event driven to accrue 123 primary events. Each participant will have an average of 24 months of follow-up period (which will range 1 to 3 years).


Inclusion criteria

•Age greater than or equal to 45 years, at the time of signing the informed consent •Previous intracranial hemorrhage (symptomatic, spontaneous and non-traumatic intraparenchymal, intraventricular, and/or Convexal subarachnoid hemorrhage cSAH, and symptomatic spontaneous or non-penetrating traumatic subdural hemorrhages) on or off antithrombotic therapy (Table 2) •Documented atrial fibrillation (paroxysmal, persistent, permanent) •CHA2DS2-VASc score greater than or equal to 2


Exclusion criteria

•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) •Traumatic or aneurysmal cSAH •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 or other creatinine clearance following local product monograph (Canada < 30mL/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 •Estimated inability to adhere to study procedures •Pregnancy or breastfeeding •Estimated life expectancy < 6 months at the time of enrollment •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)



Primary outcome(s)

1.

Stroke composite of ischemic, hemorrhagic, and unspecified

[

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

]
2.

Primary safety outcome Major hemorrhage as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria

[

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

]
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Secondary outcome(s)

1.

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)

]
2.

Cardiovascular death: Death related to cardiovascular cause

[

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

]
3.

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)

]
4.

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)

]
5.

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)

]
6.

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)

]
7.

Modified Rankin Scale: mRS as measured at 12 month visit

[

12 months

]
8.

Secondary safety outcome 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)

]
9.

Secondary safety outcome 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)

]
10.

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)

]
11.

Secondary safety outcome Hospitalization for any cause: Minimum of one overnight stay in hospital.

[

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

]
12.

Secondary safety outcome Cardiovascular death: Death related to cardiovascular cause.

[

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

]
13.

Secondary safety outcome 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)

]
14.

Secondary safety outcome 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.

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

]
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Target number/sample size

50 (25 in each arm) in Sri Lanka (Global 1200, 600 in each arm)


Countries of recruitment

Argentina, Austria, Belgium, Canada, China, Czech Republic, Denmark, Egypt, Germany, Greece, India, Italy, Nepal, Portugal, Slovakia, Spain, Sri Lanka, Switzerland, Taiwan, Province of China, United Kingdom, United States


Anticipated start date

2022-03-31


Anticipated end date

2023-07-30


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Hamilton Health Sciences, through its Population Health Research Institute


Regulatory approvals

Pending



State of Ethics Review Approval


Status

Approved


Date of Approval

2022-01-11


Approval number

P/142/10/2021


Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Institutional Address:Ethics Review Committee, Faculty of Medicine, University of Kelaniya, P.O Box 6, Thalagolla Road, Ragama, Sri Lanka
Telephone:+94 11 2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr.Bimsara Senanayake
Consultant Neurologist
National Hospital of Sri-Lanka Colombo 10

0773046096

bimsaras@sltnet.lk

Contact Person for Public Queries

Dr.Bimsara Senanayake
Consultant Neurologist
National Hospital of Sri-Lanka Colombo 10

0773046096

bimsaras@sltnet.lk


Primary study sponsor/organization

Hamilton Health Sciences, through its Population Health Research Institute

Hamilton Health Sciences, through its Population Health Research Institute 237 Barton Street East Hamilton, ON L8L 2X2 Canada
527-4322

ENRICH-AF@phri.ca

Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description

N/A


Study protocol available

No


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results