Clinical Trials List
Protocol NumberDSE-EDO-01-16-EU
2017-04-01 - 2018-12-31
Phase III
Terminated5
ICD-10I48.91
Unspecified atrial fibrillation
ICD-9427.31
Atrial fibrillation
A PROSPECTIVE, RANDOMIZED, OPEN-LABEL, BLINDED ENDPOINT EVALUATION (PROBE) PARALLEL GROUP STUDY COMPARING EDOXABAN VS. VKA IN SUBJECTS UNDERGOING CATHETER ABLATION OF NON-VALVULAR ATRIAL FIBRILLATION (ELIMINATE-AF)
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Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Huang-Chung Chen Division of Cardiovascular Diseases
- 陳勉成 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Shih-Lin Chang Division of Cardiovascular Diseases
- Shih-Ann Chen Division of Cardiovascular Diseases
- 胡瑜峰 Division of Cardiovascular Diseases
- Li-Wei Lo Division of Cardiovascular Diseases
- Fa-Po Chung Division of Cardiovascular Diseases
- Ting-Yung Chang Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- JIN–LONG HUANG Division of Cardiovascular Diseases
- 吳茲睿 Division of Cardiovascular Diseases
- 廖英傑 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 林晏年 Division of Cardiovascular Diseases
- 林圀宏 Division of Cardiovascular Diseases
- Jan-Yow Chen Division of Cardiovascular Diseases
- 吳宏彬 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Non-valvular atrial fibrillation (AF)
Objectives
Primary efficacy objective:To compare descriptively the incidence of the composite of all-cause death, stroke (ischemic, hemorrhagic, or undetermined) and Major Bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) in the doxaban group against the vitamin Kantagonist (VKA) group in subjects undergoing catheter ablation of atrial fibrillation (AF) in the period from the end of the catheter ablation procedure to Day 90/end-of-treatment (EOT).
Primary safety objective:To compare descriptively the incidence of Major Bleeding (ISTHdefinition) in the edoxaban group against the VKA group in the period
from date of first intake of study medication to Day 90/EOT.
Test Drug
Edoxaban (DU-176b)
Active Ingredient
Edoxaban tosylate (DU-176b)
Dosage Form
tablet
Dosage
15, 30, 60
Endpoints
Primary safety objective:
To compare descriptively the incidence of Major Bleeding (ISTH
definition) in the edoxaban group against the VKA group in the period
from date of first intake of study medication to Day 90/EOT.
Secondary objectives:
In subjects undergoing catheter ablation of AF, to compare
descriptively the edoxaban group against the VKA group, with
regards to the incidence of the following efficacy endpoints as listed
below:
Composite of all-cause death, stroke (ischemic, hemorrhagic,
or undetermined, according to alternative definition (1); see
Section 7.4.2. for details) and Major Bleeding (ISTH
definition)
Composite of stroke (ischemic, hemorrhagic, or undetermined)
systemic embolic events (SEE), and cardiovascular (CV)
mortality
Composite of stroke (ischemic, hemorrhagic, or undetermined)
SEE, and all-cause mortality
Composite of stroke (ischemic, hemorrhagic, or undetermined)
and transient ischemic attack (TIA)
Stroke (ischemic, hemorrhagic, or undetermined)
Stroke (ischemic)
Stroke (hemorrhagic)
Stroke (undetermined)
SEE
TIA
Fatal stroke (ischemic, hemorrhagic, or undetermined)
Non-fatal stroke (ischemic, hemorrhagic, or undetermined)
Disabling stroke (ischemic, hemorrhagic, or undetermined)
Non-disabling stroke (ischemic, hemorrhagic, or
undetermined)
To compare descriptively the edoxaban group against the VKA group,
with regards to the incidence of the following safety endpoints as
listed below:
Major Bleeding (defined by Thrombolysis in Myocardial
Infarction [TIMI], Bleeding Academic Research Consortium
[BARC] 2 or higher)
Major and Clinically Relevant Non-Major (CRNM) Bleeding
(ISTH definition)
CRNM Bleeding (ISTH definition)
Minor Bleeding (ISTH definition)
Any Bleeding
Intracranial hemorrhage (ICH)
Life-threatening bleeding
Fatal Major Bleeding (ISTH definition)
Non-fatal Major Bleeding (ISTH definition)
Fatal Major Bleeding (defined by TIMI, BARC [2 or higher])
Non-fatal Major Bleeding (defined by TIMI, BARC [2 or
higher])
Safety parameters such as adverse events (AEs), serious
adverse events (SAEs), laboratory parameters, electrocardiogram (ECG) and vital signs.
Other objectives:
To compare descriptively the edoxaban group against the VKA group,
with regards to the following:
Relevant Health Economics Outcome Research (HEOR)
parameters:
o Number of subjects with cancellation of the ablation
procedure due to inadequate anticoagulation
o Number of hospital admissions due to CV causes
(beyond ablation procedure), including but not limited
to overall, for bleeding, SEE, venous thrombosis, etc.
Remark: Hospital admissions due to CV causes
include, but are not limited to Emergency Department
(ED), Intensive Care Unit (ICU), CV ward.
o Mean length of stay associated with the different type
of hospital admissions, such as ED, ICU and CV wards
o Additional outpatient physician or nurse visits that are
CV event related outside scheduled visits as defined by
study protocol
Silent cerebral lesions (SCL) as defined by Diffusion
Weighted Magnetic Resonance Imaging (DW-MRI) post
ablation procedure (at preselected centers)
Cardiac and anticoagulation markers
To compare descriptively the incidence of Major Bleeding (ISTH
definition) in the edoxaban group against the VKA group in the period
from date of first intake of study medication to Day 90/EOT.
Secondary objectives:
In subjects undergoing catheter ablation of AF, to compare
descriptively the edoxaban group against the VKA group, with
regards to the incidence of the following efficacy endpoints as listed
below:
Composite of all-cause death, stroke (ischemic, hemorrhagic,
or undetermined, according to alternative definition (1); see
Section 7.4.2. for details) and Major Bleeding (ISTH
definition)
Composite of stroke (ischemic, hemorrhagic, or undetermined)
systemic embolic events (SEE), and cardiovascular (CV)
mortality
Composite of stroke (ischemic, hemorrhagic, or undetermined)
SEE, and all-cause mortality
Composite of stroke (ischemic, hemorrhagic, or undetermined)
and transient ischemic attack (TIA)
Stroke (ischemic, hemorrhagic, or undetermined)
Stroke (ischemic)
Stroke (hemorrhagic)
Stroke (undetermined)
SEE
TIA
Fatal stroke (ischemic, hemorrhagic, or undetermined)
Non-fatal stroke (ischemic, hemorrhagic, or undetermined)
Disabling stroke (ischemic, hemorrhagic, or undetermined)
Non-disabling stroke (ischemic, hemorrhagic, or
undetermined)
To compare descriptively the edoxaban group against the VKA group,
with regards to the incidence of the following safety endpoints as
listed below:
Major Bleeding (defined by Thrombolysis in Myocardial
Infarction [TIMI], Bleeding Academic Research Consortium
[BARC] 2 or higher)
Major and Clinically Relevant Non-Major (CRNM) Bleeding
(ISTH definition)
CRNM Bleeding (ISTH definition)
Minor Bleeding (ISTH definition)
Any Bleeding
Intracranial hemorrhage (ICH)
Life-threatening bleeding
Fatal Major Bleeding (ISTH definition)
Non-fatal Major Bleeding (ISTH definition)
Fatal Major Bleeding (defined by TIMI, BARC [2 or higher])
Non-fatal Major Bleeding (defined by TIMI, BARC [2 or
higher])
Safety parameters such as adverse events (AEs), serious
adverse events (SAEs), laboratory parameters, electrocardiogram (ECG) and vital signs.
Other objectives:
To compare descriptively the edoxaban group against the VKA group,
with regards to the following:
Relevant Health Economics Outcome Research (HEOR)
parameters:
o Number of subjects with cancellation of the ablation
procedure due to inadequate anticoagulation
o Number of hospital admissions due to CV causes
(beyond ablation procedure), including but not limited
to overall, for bleeding, SEE, venous thrombosis, etc.
Remark: Hospital admissions due to CV causes
include, but are not limited to Emergency Department
(ED), Intensive Care Unit (ICU), CV ward.
o Mean length of stay associated with the different type
of hospital admissions, such as ED, ICU and CV wards
o Additional outpatient physician or nurse visits that are
CV event related outside scheduled visits as defined by
study protocol
Silent cerebral lesions (SCL) as defined by Diffusion
Weighted Magnetic Resonance Imaging (DW-MRI) post
ablation procedure (at preselected centers)
Cardiac and anticoagulation markers
Inclution Criteria
Inclusion Criteria
Subjects must satisfy all of the following criteria to be included in the study:
1. Male or female at least 18 years of age with documented history of paroxysmal (lasting
≤7 days), persistent (lasting >7 days but ≤12 months) or long-standing [long-lasting]
persistent (>12 months) non-valvular AF. Duration of AF can be confirmed by any
electrical tracing or a recording in the subject’s medical records (e.g., medical chart,
hospital discharge summary).
2. Subject is eligible and is scheduled for either radiofrequency (RF) or cryoballoon catheter
ablation (both first and repeated procedure included).
3. Signed ICF.
Subjects must satisfy all of the following criteria to be included in the study:
1. Male or female at least 18 years of age with documented history of paroxysmal (lasting
≤7 days), persistent (lasting >7 days but ≤12 months) or long-standing [long-lasting]
persistent (>12 months) non-valvular AF. Duration of AF can be confirmed by any
electrical tracing or a recording in the subject’s medical records (e.g., medical chart,
hospital discharge summary).
2. Subject is eligible and is scheduled for either radiofrequency (RF) or cryoballoon catheter
ablation (both first and repeated procedure included).
3. Signed ICF.
Exclusion Criteria
Exclusion Criteria
Subjects who meet any of the following criteria will be disqualified from entering the study:
1. AF considered to be of a transient or reversible nature (such as in myocarditis, postsurgery, ionic disturbances, thyrotoxicosis, pneumonia, severe anemia etc.).
2. Subject post stroke, or with a systemic thromboembolic event within the past 6 months prior to randomization.
3. Subject has a thrombus in the left atrial appendage (LAA), left atrium (LA), left ventricle (LV), or aorta, or an intracardial mass.
4. Subject had a myocardial infarction (MI) within the 2 months prior to randomization or coronary artery bypass graft (CABG) surgery within 3 months prior to the
randomization.
5. Subject has signs of bleeding, history of clinically-relevant bleeding according to ISTH, or conditions associated with high risk of bleeding such as past history of intracranial (spontaneous or traumatic), or spontaneous intraocular, spinal, retroperitoneal, or intra-articular bleeding; overt gastrointestinal (GI) bleeding or active ulcer within the previous year; recent severe trauma, major surgery, or deep organ biopsy; active infective endocarditis; uncontrolled hypertension (blood pressure [BP] above 170/100 mmHg); or hemorrhagic disorder including known or suspected hereditary or acquired bleeding or coagulation disorder in the last 12 months prior to randomization.
6. Subjects with mechanical heart valves, subjects with moderate to severe mitral stenosis and subjects who have new implantation (within 3 months prior to randomization) of a bioprosthetic heart valve, with or without AF.
7. Subjects with a history of LAA occlusion/exclusion (either by surgery or by a
procedure).
8. Subjects with any contraindication for edoxaban, VKA, low molecular weight heparin (LMWH), heparin therapy.
9. Subjects receiving dual antiplatelet therapy (DAPT, i.e., aspirin and P2Y12 antagonist) or planned to receive DAPT during the study
10. Subjects who require chronic use of medicines affecting hemostasis such as higher doses of aspirin (acetylsalicylic acid [ASA]) (ASA up to 100 mg per day allowed) or chronic oral or parenteral intake of non-aspirin non-steroidal anti-inflammatory drugs (NSAID) on ≥4 days/week (use of NSAIDs via other routes is not restricted)
11. Subjects with active liver disease or persistent (confirmed by repeat assessments at least a week apart) elevation of liver enzymes/bilirubin:
― Alanine transaminase (ALT) or aspartate transaminase (AST) ≥2 times the upper limit of normal (ULN) ― Total bilirubin (TBL) ≥1.5 times the ULN (subjects whose elevated TBL is due to known Gilbert’s syndrome may be included in the study)
― Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.
12. Subjects with kidney failure (calculated creatinine clearance [CrCL] <15 mL/min).
13. Subjects with hemoglobin <10 g/dL or platelet count <100,000 cells/µL or white blood cell (WBC) count <3000 cells/µL.
14. Subjects with pre-planned invasive diagnostic or therapeutic procedures/interventions (other than endoscopy) during the study period in which bleeding is anticipated.
15. Participation in any other interventional trial (subjects who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period).
16. Previous randomization in this study.
17. Female subjects of childbearing potential without using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least 3 months prior to the start of this study [Visit 1]). Females taking oral contraceptives should have been on therapy for at least 3 months. Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable),
and double barrier methods such as condoms or diaphragms with spermicidal gel or
foam.
18. Pregnant or breast-feeding subjects.
19. Subjects with the following diagnoses or situations:
- Active cancer undergoing chemotherapy, radiation or major surgery within the next 5
months
- Significant active/uncontrolled concurrent medical illness
- Life expectancy <6 months.
20. Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude,
inability to return for subsequent visits, and/or otherwise considered by the Investigator
to be unlikely to complete the study).
21. Subjects with a known drug or alcohol dependence within the past 12 months prior to randomization as judged by the Investigator.
22. Subjects with any condition that, in the opinion of the Investigator, would place the subject at increased risk of harm if he/she participated in the study.
23. Planned procedure using laser catheter ablation or other forms of catheter ablation different from RF or cryoballoon (i.e. high intensity focused ultrasound [HIFU], microwaves, hot balloon, etc).
Subjects who meet any of the following criteria will be disqualified from entering the study:
1. AF considered to be of a transient or reversible nature (such as in myocarditis, postsurgery, ionic disturbances, thyrotoxicosis, pneumonia, severe anemia etc.).
2. Subject post stroke, or with a systemic thromboembolic event within the past 6 months prior to randomization.
3. Subject has a thrombus in the left atrial appendage (LAA), left atrium (LA), left ventricle (LV), or aorta, or an intracardial mass.
4. Subject had a myocardial infarction (MI) within the 2 months prior to randomization or coronary artery bypass graft (CABG) surgery within 3 months prior to the
randomization.
5. Subject has signs of bleeding, history of clinically-relevant bleeding according to ISTH, or conditions associated with high risk of bleeding such as past history of intracranial (spontaneous or traumatic), or spontaneous intraocular, spinal, retroperitoneal, or intra-articular bleeding; overt gastrointestinal (GI) bleeding or active ulcer within the previous year; recent severe trauma, major surgery, or deep organ biopsy; active infective endocarditis; uncontrolled hypertension (blood pressure [BP] above 170/100 mmHg); or hemorrhagic disorder including known or suspected hereditary or acquired bleeding or coagulation disorder in the last 12 months prior to randomization.
6. Subjects with mechanical heart valves, subjects with moderate to severe mitral stenosis and subjects who have new implantation (within 3 months prior to randomization) of a bioprosthetic heart valve, with or without AF.
7. Subjects with a history of LAA occlusion/exclusion (either by surgery or by a
procedure).
8. Subjects with any contraindication for edoxaban, VKA, low molecular weight heparin (LMWH), heparin therapy.
9. Subjects receiving dual antiplatelet therapy (DAPT, i.e., aspirin and P2Y12 antagonist) or planned to receive DAPT during the study
10. Subjects who require chronic use of medicines affecting hemostasis such as higher doses of aspirin (acetylsalicylic acid [ASA]) (ASA up to 100 mg per day allowed) or chronic oral or parenteral intake of non-aspirin non-steroidal anti-inflammatory drugs (NSAID) on ≥4 days/week (use of NSAIDs via other routes is not restricted)
11. Subjects with active liver disease or persistent (confirmed by repeat assessments at least a week apart) elevation of liver enzymes/bilirubin:
― Alanine transaminase (ALT) or aspartate transaminase (AST) ≥2 times the upper limit of normal (ULN) ― Total bilirubin (TBL) ≥1.5 times the ULN (subjects whose elevated TBL is due to known Gilbert’s syndrome may be included in the study)
― Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.
12. Subjects with kidney failure (calculated creatinine clearance [CrCL] <15 mL/min).
13. Subjects with hemoglobin <10 g/dL or platelet count <100,000 cells/µL or white blood cell (WBC) count <3000 cells/µL.
14. Subjects with pre-planned invasive diagnostic or therapeutic procedures/interventions (other than endoscopy) during the study period in which bleeding is anticipated.
15. Participation in any other interventional trial (subjects who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period).
16. Previous randomization in this study.
17. Female subjects of childbearing potential without using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least 3 months prior to the start of this study [Visit 1]). Females taking oral contraceptives should have been on therapy for at least 3 months. Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable),
and double barrier methods such as condoms or diaphragms with spermicidal gel or
foam.
18. Pregnant or breast-feeding subjects.
19. Subjects with the following diagnoses or situations:
- Active cancer undergoing chemotherapy, radiation or major surgery within the next 5
months
- Significant active/uncontrolled concurrent medical illness
- Life expectancy <6 months.
20. Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude,
inability to return for subsequent visits, and/or otherwise considered by the Investigator
to be unlikely to complete the study).
21. Subjects with a known drug or alcohol dependence within the past 12 months prior to randomization as judged by the Investigator.
22. Subjects with any condition that, in the opinion of the Investigator, would place the subject at increased risk of harm if he/she participated in the study.
23. Planned procedure using laser catheter ablation or other forms of catheter ablation different from RF or cryoballoon (i.e. high intensity focused ultrasound [HIFU], microwaves, hot balloon, etc).
The Estimated Number of Participants
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Taiwan
99 participants
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Global
620 participants
