* To assess the effect of Edoxaban versus vitamin K antagonist (VKA) on net adverse clinical events (NACE), i.e., the composite of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SEE), valve thrombosis, and…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy endpoints:
* NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE,
valve thrombosis, and major and minor bleeding per TIMI definitions
* NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE,
valve thrombosis, and major bleeding (Bleeding Academic Research Consortium
[BARC] 3 or 5 definition)
* NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE,
valve thrombosis, and major and moderate bleeding (Global Utilization of
Streptokinase And Tissue Plasminogen Activator For Occluded Coronary arteries
[GUSTO] definition)
* Major Adverse Cardiac Events (MACE), defined as the composite of
all-cause death (excluding adjudicated non-cardiac death), MI, or repeat
coronary revascularization of the target lesion
* Major Adverse Cardiac and Cerebrovascular Events (MACCE), defined as the
composite of all-cause death (excluding adjudicated non-cardiac
death), MI, stroke (ischemic, hemorrhagic, or undetermined), or repeat coronary
revascularization of the target lesion
* Cardiovascular mortality
* Stroke (ischemic, hemorrhagic, or undetermined)
* Stroke (ischemic)
* Stroke (hemorrhagic)
* Stroke (undetermined)
* Fatal stroke (ischemic, hemorrhagic, or undetermined)
* Non-fatal stroke (ischemic, hemorrhagic, or undetermined)
* SEE
* Myocardial Infarction
* Valve thrombosis
Safety endpoints:
* Bleeding defined as TIMI major and minor, BARC 3 or 5, and GUSTO moderate or
severe
* Bleeding defined as ISTH major and CTNM, TIMI major/minor bleeds or requiring
medical attention, BARC 2, 3 or 5, and GUSTO moderate or severe
* Bleeding defined as ISTH, CRNM, TIMI minor or requiring medical attention,
BARC 2, and GUSTO moderate
* All bleeding that are not ISTH major, CRNM, TIMI minimal, BARC 1
non-actionable, and GUSTO mild
* Any bleeding
* Intracranial hemorrhage
* Life-threatening bleeding
* Fatal bleeding (fulfilling the ISTH major bleeding definition)
* Non-fatal major bleeding (ISTH definition)
* All-cause mortality
* Cardiovascular mortality
* Safety parameters such as (serious) adverse events, laboratory parameters,
ECG and vital signs
Secondary outcome
* Number of hospital admissions, defined as * 24 h stay in the hospital, due to
cardiovascular causes (post TAVI and non-TAVI procedure related), including but
not limited to overall, for bleeding, SEE, venous thrombosis, shock,
arrhythmia, cardiac rupture, stroke, aneurysms, stent occlusions, etc.)
o Note: Hospital admissions due to cardiovascular causes include, but are not
limited to Emergency Department (ED), Intensive Care Unit (ICU), cardiovascular
ward
* Treatment satisfaction as assessed by the Perception Anticoagulant Treatment
Questionnaire (PACT-Q)
* Health related quality of life as assessed by the EuroQoL (EQ-5D-5L)
Questionnaire
* Biomarker of hemostasis such as but not limited to markers of coagulation and
aggregation (sub-study) such as whole blood clotting time (WBCT),
thrombelasto-graphy (TEG), multiple electrode aggregometry (MEA)
Background summary
Degenerative aortic valve stenosis is the second most common valvular disorder
in
Europe and in the United States. Transcatheter aortic valve implantation (TAVI)
is a life-saving
procedure for patients with severe aortic stenosis and high risk for surgery.
Bleeding complications and cerebrovascular events following TAVI are a matter
of concern. Patients undergoing TAVI are elder, frail, and at high risk for
both stroke and bleeding. This risk increases exponentially in patients with
atrial fibrillation or other indications to chronic anticoagulation therapy.
Balancing the risk of both bleeding and thrombotic events in this population is
challenging. Moreover, optimal anti-thrombotic therapy after TAVI is still
unknown. Therefore the use of a direct factor Xa inhibitor such as Edoxaban in
patients undergoing TAVI may be an attractive option in order to prevent
thromboembolic and bleeding events.
Study objective
* To assess the effect of Edoxaban versus vitamin K antagonist (VKA) on net
adverse clinical events (NACE), i.e., the composite of all-cause death,
myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SEE),
valve thrombosis, and major bleeding (International Society on Thrombosis and
Haemostasis [ISTH] definition).
* To assess the effect of Edoxaban versus VKA on major bleeding (ISTH
definition).
Study design
This is a multinational, multicenter, prospective, randomized, open-label study
with blinded evaluation of endpoints (PROBE) parallel group study comparing
Edoxaban with VKA in subjects with AF having undergone TAVI. Critical events
will be adjudicated by an independent Clinical Event Committee (CEC). An
independent Data and Safety Monitoring Board (DSMB) is responsible for
monitoring safety during the study.
Intervention
* Edoxaban-based regimen:
Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects
(dose reduction criteria according to locally approved label).
* VKA-based regimen:
The VKA of choice (any locally approved), dose-adjusted throughout the
study for target international normalized ratio (INR) between 2.0 to 3.0
(numbers inclusive).
Study burden and risks
The main risk of treatment with Edoxaban is bleeding. This is similar to the
risk of standard of care treatment with VKA. Therefore, the main "risks" of
participation in the study are more the additional burden study participation
entails (blood draws, time input, etc.).
Overall, edoxaban has an adequately characterized positive benefit-risk ratio
in large and representative populations globally in patients with NVAF and VTE,
demonstrating efficacy in the overall populations and subgroups in conjunction
with a favorable bleed profile as well as demonstrating its effectiveness in a
dose-dependent manner for VTE prevention after orthopedic surgery such as hip
or knee
replacement. Additional advantages of edoxaban are its QD dosing, dose
reduction strategies to minimize the risk of bleeding with preserved efficacy
and no necessity for constant monitoring of therapy.
Mount Airy Road 221
Basking Ridge NJ07920
US
Mount Airy Road 221
Basking Ridge NJ07920
US
Listed location countries
Age
Inclusion criteria
Subjects must satisfy all of the following criteria to be included in the
study:, 1. Successful TAVI via transvascular access route such as to the
femoral, carotid, axillary, and subclavian arteries. Other access routes need
prior approval per majority vote from 3 members of the Executive Committee
(both Global Lead Investigators and the Daiichi Sankyo Medical Lead or his/her
designee); success is defined as:, a. Correct positioning of a single
prosthetic heart valve into the proper anatomical location
b. Presence of all 3 conditions post TAVI
i. Mean aortic valve gradient <20 mm Hg
ii. Peak transvalvular velocity <3.0 m/s
iii. Aortic valve regurgitation of 2 or less
c. No clinically overt stroke
d. No uncontrolled bleeding at time of randomization, 2. Indication for chronic
OAC
a. Documented pre-existing AF
b. New onset AF (e.g. >30 seconds documented by ECG), 3. Provision of signed
informed consent, 4. Age *18 years
Exclusion criteria
1. Conditions with a high risk of bleeding
This may include but is not limited to: active peptic ulcer with upper
gastrointestinal bleeding within last 90 days prior to randomization,
malignancy at high risk of bleeding, major intraspinal or intracerebral
vascular abnormalities, recent unresolved brain or spinal injury, or spinal
surgery (recent = within the last 90 days prior to randomization), any
intracranial hemorrhage, known or suspected esophageal varices, arteriovenous
malformations, or clinically relevant vascular aneurysms., 2. Other known
bleeding diatheses, 3. Conditions that make it difficult for the subject to
swallow the study medication , 4. Serious unresolved periprocedural
complications, 5. Any contraindications to EITHER Edoxaban OR VKA, per local
label; this includes hypersensitivity to the active ingredient, to any of the
excipients, or any of the components of the study medications, 6. Concomitant
treatment with other antithrombotic agents, ASA >100 mg/day, fibrinolytic
therapy, or chronic (> 4 days/week) use of nonsteroidal antiinflammatory drugs
(NSAIDs); however, NSAID patches are permitted, 7. Requirement for
dual-antiplatelet therapy (DAPT) at randomization that will be indicated for
more than 3 months beyond the first OAC dose., 8. Treatment with other
investigational drugs (i.e. non-approved) or devices within 30 days before
enrollment or planned use of investigational drugs or devices during the study,
For full list of Exclusion criteria: Refer to Protocol, section: 4.2
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003930-26-NL |
| ClinicalTrials.gov | NCT02943785 |
| CCMO | NL60356.078.17 |