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. |
Aortastenose waarvoor een transkatheter aortaklepimplantatie is verricht. |
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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. |
Aortakleplijden waarvoor een transkatheter aortaklepimplantatie is verricht. |
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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 |
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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1. Het bepalen van de veiligheid van het omitteren van clopidogrel vergeleken met een behandelstrategie bestaande uit aspirine + clopidogrel gedurende 1 jaar follow-up in patiënten zonder een indicatie voor OAC na TAVI (Cohort A); 2. Het bepalen van de veiligheid van het omitteren van clopidogrel vergeleken met een behandelstrategie bestaande uit OAC + clopidogrel gedurende 1 jaar follow-up in patiënten met een indicatie voor OAC na 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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1. Het bepalen van het netto klinisch voordeel van het omitteren van clopidogrel vergeleken met een behandelstrategie bestaande uit aspirine + clopidogrel gedurende 1 jaar follow-up in patiënten zonder een indicatie voor OAC na TAVI (Cohort A); 2. Het bepalen van het netto klinisch voordeel van het omitteren van clopidogrel vergeleken met een behandelstrategie bestaande uit OAC + clopidogrel gedurende 1 jaar follow-up in patiënten met een indicatie voor OAC na TAVI (Cohort B); 3. Het bepalen van de effectiviteit van het omitteren van clopidogrel gedurende 1 jaar follow-up in patiënten met en zonder een indicatie voor OAC (Cohort A en B). 4. Het bepalen van de effecten van genetische variaties van CYP2C19 and PTGS2 op klinische uitkomsten. |
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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. |
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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. |
Cohort A 1. Patiënt heeft informed consent getekend.
Cohort B 1. Nood aan lange termijn orale anticoagulantia; 2. Patiënt heeft informed consent getekend. |
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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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Cohort A 1. Nood aan lange termijn orale anticoagulantia; 2. Drug-eluting stent implantatie binnen 3 maanden voorafgaand aan de TAVI procedure; 3. Bare-metal stent implantatie binnen 1 maand voorafgaand aan de TAVI procedure; 4. Allergie of intolerantie voor aspirine of clopidogrel.
Cohort B 1. Drug-eluting stent implantatie binnen 3 maanden voorafgaand aan de TAVI procedure; 2. Bare-metal stent implantatie binnen 1 maand voorafgaand aan de TAVI procedure; 3. Gebruik van een non-vitamine K orale anticoagulantium (NOAC); 3. Allergie of intolerantie voor clopidogrel. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary safety outcome is defined non-procedure related bleeding an all bleeding. |
Primair veiligheidseindpunt is gedefinieerd als non-procedure gerelateerde bloedingen en alle bloedingen. |
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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. |
Secundaire effectiviteitseindpunt is een composiet van cardiovasculaire mortaliteit, non-procedure grelateerde bloedingen, cerebrovasculair accident, en myocardinfarct.
Secundaire netto klinisch voordeel eindpunt is een composiet van cardiovasculaire mortaliteit, ischemisch cerebrovasculair accident, en myocardinfarct. |
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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 | 8 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |