E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aortic stenosis for which a transcatheter aortic valve implantation (TAVI) is performed. |
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E.1.1.1 | Medical condition in easily understood language |
Aortic stenosis for which a transcatheter aortic valve implantation (TAVI) is performed. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002906 |
E.1.2 | Term | Aortic stenosis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 |
1. To investigate the safety of omission of clopidogrel compared to a strategy using aspirin + clopidogrel during 1 year follow-up in patients without an indication for OAC after TAVI (Cohort A); 2. To investigate the safety of omission of clopidogrel compared to a strategy using OAC + clopidogrel during 1 year follow-up in patients with an indication for OAC after TAVI (Cohort B).
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E.2.2 | Secondary objectives of the trial |
1. To investigate the net-clinical benefit of omission of clopidogrel compared to a strategy using aspirin + clopidogrel during 1 year follow-up in patients without an indication for OAC after TAVI (Cohort A); 2. To investigate the net-clinical benefit of omission of clopidogrel compared to a strategy using OAC + clopidogrel during 1 year follow-up in patients with an indication for OAC after TAVI (Cohort B); 3. To investigate the efficacy of omission of clopidogrel during 1 year follow-up in patients with and without an indication for OAC after TAVI (Cohort A + B); 4. To investigate the effects of genetic variations of CYP2C19 and PTGS2 on clinical outcomes.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. SUBSTUDY #1: Myocardial and renal damage in patients undergoing TAVI. The primary objective of this prospective pilot cohort study is to evaluate the effectiveness of proteinuria as an early detection for renal function and to determine the predictive role on outcome. The secondary objective is to identify the role of clopidogrel on renal and myocardial damage. Furthermore, we aim to identify peri-procedural changes that may contribute to renal and myocardial insult to gather more insight in aetiology and possible preventive strategies. 2. SUBSTUDY #2: The relation between macro- and microvascular variables and outcome in patients undergoing TAVI. To study the characteristics of low cardiac output during TAVI and the relation of tissue hypoperfusion with postprocedural inflammation and acute kidney injury. 3. SUBSTUDY #3: An AMCerebral MRI substudy. The main objective of the AMC substudy is to assess the additive value of clopidogrel to aspirin or OAC, by assessing the of occurrence silent cerebral infarcts on diffusion weighted magnetic resonance (MRI) between treatment groups, as a surrogate marker for cerebrovascular events. 3. SUBSTUDY #4: EchoNavigator reducing renal damage in TAVI patients. The primary objective of this prospective pilot cohort substudy is to evaluate if the use of EchoNavigator can facilitate in the reduction of contrast volume and fluoroscopy reduction during TAVI procedures, in order to reduce renal damage in TAVI patients. |
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E.3 | Principal inclusion criteria |
Cohort A 1. Patient has provided written informed consent.
Cohort B 1. Need for long-term oral anticoagulation; 2. Patient has provided written informed consent. |
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E.4 | Principal exclusion criteria |
Cohort A 1. Need for long-term oral anticoagulation. 2. Drug-eluting stent implantation within 3 months prior to TAVI procedure. 3. Bare-metal stent implantation within 1 month prior to TAVI procedure. 4. Allergy or intolerance or contraindication to aspirin or clopidogrel.
Cohort B 1. Drug-eluting stent implantation within 3 months prior to TAVI procedure. 2. Bare-metal stent implantation within 1 month prior to TAVI procedure. 3. Use of non-vitamin K oral anticoagulation (NOAC). 4. Allergy or intolerance or contraindication to OAC or clopidogrel.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary safety outcome is defined as non-procedure related bleeding and all bleeding. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy outcome is a composite of cardiovascular mortality, non-procedure related bleeding, stroke, and myocardial infarction.
Secondary net-clinical benefit outcome is a composite of cardiovascular mortality, ischaemic stroke, and myocardial infarction. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | Yes |
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
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |