E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
aortic stenosis |
aortastenose |
|
E.1.1.1 | Medical condition in easily understood language |
narrowing of the aortic heart valve |
vernauwing van de aortaklep |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether edoxaban affects the incidence of aortic valve leaflet thickening after TAVI as assessed by cardiac 4DCT-scan after 3 months treatment. |
|
E.2.2 | Secondary objectives of the trial |
To investigate whether treatment with edoxaban affects transprosthetic gradients (i.e. change in transprosthetic gradient between TTE at discharge and at 1 year) after TAVI. And to investigate the effect on the incidence of stage ≥2 bioprosthetic valve dysfunction at 1 year as defined by the VARC-3 consensus.
To investigate the safety of edoxaban treatment in patients undergoing TAVI -with no formal OAC indication- on net adverse clinical outcomes after 1 month, 3 months and one year; i.e.: the composite of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism, valve thrombosis and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) and every endpoint separately including any neurological event (minor/disabling stroke and TIA)
To investigate the effect of edoxaban treatment in patients undergoing TAVI -with no formal OAC indication- on major bleeding at 1 month, 3 months and one year |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients completed successful elective TAVI for severe aortic valve stenosis with any commercially-available transcatheter heart valve (THV). o Correct positioning of a single prosthetic heart valve into the proper anatomical location o Device success, defined by Mean aortic valve gradient < 20 mmHg Peak transvalvular velocity <3.0 m/s Aortic valve regurgitation of 2 or less • No periprocedural complications o No overt stroke o No uncontrolled bleeding o No major vascular complication defined by the VARC-3 consensus o No cardiac structural complication defined by the VARC-3 consensus • No formal indication for oral anticoagulation o Prevention of thromboembolic complications in patients with atrial fibrillation o Prevention for recurrent venous thromboembolism o Prevention for recurrent pulmonary embolism |
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E.4 | Principal exclusion criteria |
• History of life-threatening or major bleeding event ≥ BARC 3b definitions within the last year • Other conditions with a high risk of bleeding o Active peptic ulcer or upper gastrointestinal bleeding within last 3 months prior to enrolment o Malignancy with high risk of bleeding o Recent unresolved brain of spinal injury o Spinal or ophthalmic surgery within last 3 months prior to enrolment o Intracranial haemorrhage o Esophagal varices o Atriovenous malformations with high risk of bleeding o Vascular aneurysms o Major intraspinal or intracerebral vascular abnormalities • Hypersensitivity or contraindications to edoxaban • Requirement for dual-antiplatelet therapy (DAPT) within 1 month prior to randomization. • Concomitant percutaneous coronary intervention (PCI) during the TAVI procedure, requiring DAPT after the procedure. • Renal impairment defined as by dialysis-dependency or GFR < 30 mL/min at time of enrollment • Active bleeding or bleeding diasthesis including thrombocytopenia (platelet count < 50.000 cells/UL), thrombobasthenia, haemophilia or von Willebrand disease • Patients unable to adhere to or complete the investigational protocol for any reason including but not limited to geographical residence, psychiatric condtition or life-threatening disease • Pregnant or breast-feeding subjects • Current participation in clinical trials that potentially interfere with the current study |
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E.5 End points |
E.5.1 | Primary end point(s) |
incidence of aortic valve leaflet thickening after TAVI as assessed by cardiac 4DCT-scan after 3 months treatment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
occurrence of reduced THV leaflet motion by MSCT at 3 months of follow up. transprosthetic gradients (i.e. change in transprosthetic gradient, effective orifice area and doppler velocity index between TTE at discharge and at 1 year) after TAVI. the occurrence and increase of aortic regurgitation as determined by transthoracic echocardiography pre-discharge and at 12 months. the composite of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism, valve thrombosis and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) and every endpoint separately including any neurological event (minor/disabling stroke and TIA) To investigate the effect of edoxaban treatment in patients undergoing TAVI -with no formal OAC indication- on major bleeding at 1 month, 3 months and one year |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
one month, 3 months and 12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The trial will end when 100 subjects have reached the primary endpoint (which is 3 months after TAVI). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |