ENRICH-TAVI

JRCT ID: jRCTs071180025

Registered date:25/02/2019

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Severe aortic stenosis
• Date of first enrollment: 16/01/2020
• Target sample size: 100
• Study type: Interventional
• Intervention(s): Administer edoxaban (30mg or 60mg or 15mg /day) antithrombotic therapy for transcatheter aortic valve implantation with aortic stenosis with atrial fibrillation.

Outcome(s)

• Primary Outcome: Differences in maximal leaflet thickness between three months and 1 week after TAVI

Secondary Outcome

1) Characteristics (area, location, and%reduced leaflet motion (%ELM))of subclinical valve leaflet thrombosis 1 week and 3months after TAVI.
2) Changes of thrombus formation before and after TAVI.
1 To measure the thrombus formation area under the curve for AR-chip (AR10-AUC30), and PL-chip
(PL24-AUC10) evaluated by T-TAS. 2 To measure von Willebrand factor 3To measure anti-Xa activity
3) Differences of wall shear stress, and oscillatory shea r index analyzed by computational fluid dynamics (CFD)1week after TAVI.
4) The factors associated with the maximal leaflet thickness at 1 week and 3 months after TAVI, and the differences.
5) Number of the adverse events 3months after TAVI defined as composite of all-cause death, myocardial infarction, stroke, TIA, acute kidney injury, bleeding complication, vascular complication, new onset of conduct disorder.
-Definition of all-cause death: Based on the VARC-2 criteria
1.Death due to proximate cardiac cause (e.g. myocardial infarction, cardiac tamponade, worsening heart failure)
2.Death caused by non-coronary vascular conditions such as neurological events, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular disease
3.All procedure-related deaths, including those related to a complication of the procedure or treatment for a complication of the procedure
4.All valve-related deaths including structural or non-structural valve dysfunction or other valve-related adverse events 5.Sudden or unwitnessed death 6.Death of unknown cause
Non-cardiovascular mortality
Any death in which the primary cause of death is clearly related to another condition (e.g. trauma, cancer, suicide)
-Definition of myocardial infarction: Based on the VARC-2 criteria
Peri-procedural MI (<-72h after the index procedure)
New ischaemic symptoms , or new ischaemic signs (e.g. ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, haemodynamic instability, new pathological Q-waves in at least two contiguous leads, imaging evidence of new loss of viable myocardium or new wall motion abnormality) AND Elevated cardiac biomarkers (preferable CK-MB) within 72h after the index procedure, consisting of at least one sample post-procedure with a peak value exceeding 15* as the upper reference limit for troponin or 5* for CK-MB.a If cardiac biomarkers are increased at baseline (>99th percentile), a further increase in at least 50% post-procedure is required AND the peak value must exceed the previously stated limit Spontaneous MI (>72h after the index procedure) Any one of the following criteria
Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile URL, together with the evidence of myocardial ischaemia with at least one of the following:
Symptoms of ischaemia ECG changes indicative of new ischaemia (new ST-T changes or new left bundle branch block (LBBB)) New pathological Q-waves in at least two contiguous leads
Imaging evidence of a new loss of viable myocardium or new wall motion abnormality
Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms suggestive of myocardial ischaemia, and accompanied by presumably new ST elevation, or new LBBB, and/or evidence of fresh thrombus by coronary angiography and/or at autopsy, but death occurring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood.
-Definition of stroke and TIA: Based on the VARC-2 criteria
Stroke: duration of a focal or global neurological deficit >-24h; <24h if available neuroimaging documents a new haemorrhage or infarct; the neurological deficit results in death
TIA: duration of a focal or global neurological deficit <24h, any variable neuroimaging does not demonstrate a new haemorrhage or infarct
-Definition of acute kidney injury: Based on the VARC-2 criteria
Stage 1 Increase in serum creatinine to 150-199% (1.5-1.99 * increase compared with baseline) or increase of >-0.3 mg/dl (>-26.4 mmol/l) Urine output <0.5 ml/kg/h for >6 but<12h
Stage 2 Increase in serum creatinine to 200-299% (2.0-2.99* increase compared with baseline) or Urine output <0.5 ml/kg/h for >12 but < 24h Stage3 Increase in serum creatinine to >-300% (>3 * increase compared with baseline) serum creatinine of >-4.0 mg/dl (>-354 mmol/l) with an acute increase of at least 0.5 mg/dl (44 mmol/l) Urine output <0.3 ml/kg/h for >-24h Anuria for >-12h
-Definition of bleeding complication: Based on the VARC-2 criteria Life-threatening or disabling bleeding
Fatal bleeding Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c) Bleeding causing hypovolaemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b)
Overt source of bleeding with drop in haemoglobin >-5 g/dl or whole blood or packed red blood cells (RBCs) transfusion >-4 units (BARC type 3b) Major bleeding (BARC type 3a)
Overt bleeding either associated with a drop in the haemoglobin level of at least 3.0 g/dl or requiring transfusion of two or three units of whole blood/RBC, or causing hospitalization or permanent injury, or requiring surgery Does not meet criteria of life-threatening or disabling bleeding
Minor bleeding (BARC type 2 or 3a, depending on the severity) Any bleeding worthy of clinical mention (e.g. access site haematoma) that does not qualify as life-threatening, disabling, or major
-Definition of vascular complication: Based on the VARC-2 criteria
Major vascular complications Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, or new apical aneurysm/pseudo-aneurysm Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, haematoma, irreversible nerve injury, compartment syndrome, percutaneous closure device failure) leading to death, life-threatening or major bleedinga, visceral ischaemia, or neurological impairment Distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage The use of unplanned endovascular or surgical intervention associated with death, major bleeding, visceral ischaemia or neurological impairment Any new ipsilateral lower extremity ischaemia documented by patient symptoms, physical exam, and/or decreased or absent blood flow on lower extremity angiogram Surgery for access site-related nerve injury Permanent access site-related nerve injury Minor vascular complications
Access site or access-related vascular injury not leading to death, life-threatening or major bleedinga, visceral ischaemia, or neurological impairment Distal embolization treated with embolectomy and/or thrombectomy and not resulting in amputation or irreversible end-organ damage Any unplanned endovascular stenting or unplanned surgical intervention not meeting the criteria for a major vascular complication Vascular repair or the need for vascular repair Percutaneous closure device failure
Failure of a closure device to achieve haemostasis at the arteriotomy site leading to alternative treatment
-Definition of new onset of conduct disorder: Based on the VARC-2 criteria Implant-related new or worsened cardiac conduction disturbance block New permanent pacemaker implantation second-degree AV block third-degree AV block incomplete right bundle branch block right bundle branch block, intraventricular conduction delay, left bundle branch block, left anterior fascicular block, or left posterior fascicular block, including block requiring a permanent pacemaker implant New-onset atrial fibrillation Any new arrhythmia resulting in haemodynamic instability or requiring therapy

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. 20 years and older
2. Patients with severe aortic stenosis who are scheduled to undergo TAVI
3. Patients who need anticoagulation therapy due to atrial fibrillation
4. Patients with the informed consent

Exclude criteria

1. Patients with the contraindications of Edoxaban
(A) Patients with a history of hypersensitivity to the components of edoxaban
(B) Patients with serious bleeding symptoms
(C) Severe liver disease with blood coagulation abnormalities and clinically important bleeding risk
(D) Acute bacterial endocarditis
(E) Severe renal dysfunction (creatinine clearance less than 15 mL / min)
2. Valvular atrial fibrillation (rheumatic mitral valve stenosis or artificial valve replacement)
3.Patients who judged unsuitable for participating in the study on the following items;
(A) High bleeding risk
1). Congenital or acquired hemorrhagic disease
2). Active ulcerative digestive tract disease
3). Thrombocytopenia
4). platelet related diseases
5). History of hemorrhagic stroke within 3 months
6). Severe hypertension with poor control
7). Patients with recent surgical history (etc. brain, spinal cord, ophthalmic)
(B) Severe liver disease
(C) Pregnant women
(D) Lactating women

Related Information

• Primary Sponsor: Kenichi Tsujita
• Secondary Sponsor: Masanobu Ishii
• Source(s) of Monetary Support: DAIICHI SANKYO COMPANY