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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003361-19 | EudraCT Number |
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| Name | Class |
|---|---|
| Aarhus University Hospital Skejby | OTHER |
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A randomized clinical trial investigating the incidence and temporal dynamics of subclinical leaflet thickening by cardiac CT in transcatheter bioprosthetic aortic valves in patients randomised to different anti-thrombotic strategies. Additionally, this study aims to examine a possible association between HALT and thromboembolic events.
The NOTION-4 trial is an investigator-initiated, randomized, open label, comparative trial conducted at Rigshospitalet in Copenhagen and Skejby Sygehus in Aarhus. All adult patients that have undergone successful TAVI without contraindications for cardiac CT will be invited to participate in this study. Patients with SR and without known other indication for chronic OAC therapy will be randomized 1:1 either to lifelong ASA or to 3 months of DOAC followed by lifelong ASA. Patients with known AF will be randomized 1:1 to lifelong DOAC versus LAAC within 3 months followed by lifelong ASA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sinus rhythm - DOAC treatment | Experimental | Can either of the following anti-platelet components: dabigatran, apixaban, rivaroxaban, edoxaban or warfarin. Duration: 3 months, followed by an anti-platelet hereafter. |
|
| Sinus rhythm - Anti-platelet treatment | Active Comparator | Can be either of the following anti-platelet components: acetylsalicylic acid or clopidogrel. Duration: Lifelong |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rivaroxaban | Drug | Direct oral anticoagulants (DOAC) treatment will encompass any of the approved drugs: Rivaroxaban, Edoxaban, Dabigatranetexilat, and Apixaban (Table 1). The DOAC dosage will be adjusted according to kidney function (Table 1) and may be adjusted during the study period according to potential changes in guideline recommendations or if new-onset AF would occur in the follow-up period. The specific DOAC prescribed will be determined by the treating physician. If the patient has already been prescribed Marevan before the aortic valve intervention, the patient will continue this medication following the procedure as an oral anticoagulant treatment, which is administered according to current guidelines. |
| Measure | Description | Time Frame |
|---|---|---|
| HALT after 1 year | The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT at one year after TAVI. | At 1 year after TAVI |
| Measure | Description | Time Frame |
|---|---|---|
| Combined clinical endpoint of all-cause mortality, thromboembolic event, and life-threatening or major bleeding | Combined clinical endpoint of all-cause mortality, thromboembolic event, and life-threatening or major bleeding | At 1 year and 5 years after TAVI |
| Incidence of patients with HALT during follow up |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ole De Backer, PhD | Rigshospital, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital, Skejby | Aarhus | Denmark | ||||
| Rigshospitalet |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39374638 | Derived | Thuraiaiyah J, Jorgensen TH, Jensen JM, Fuchs A, Willemen Y, Terkelsen CJ, Kofoed KF, Sondergaard L, Norgaard BL, De Backer O. Prospective study on the impact of different antithrombotic therapies on subclinical leaflet thickening and its temporal dynamics in transcatheter aortic valves-The NOTION-4 trial. Am Heart J. 2025 Jan;279:1-8. doi: 10.1016/j.ahj.2024.10.002. Epub 2024 Oct 5. |
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| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D006349 | Heart Valve Diseases |
| D000082862 | Aortic Valve Disease |
| ID | Term |
|---|---|
| D014694 | Ventricular Outflow Obstruction |
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| ID | Term |
|---|---|
| D000069552 | Rivaroxaban |
| D001241 | Aspirin |
| D000077144 | Clopidogrel |
| C552171 | edoxaban |
| D000069604 | Dabigatran |
| C522181 | apixaban |
| D014859 | Warfarin |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
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| Acetylsalicylic acid | Drug | Antiplatelets decrease platelet aggregation and inhibit thrombus formation. In NOTION-4 acetylsalicylic acid (75 mg once a day) is used as first line choice. For participants who are allergic to acetylsalicylic acid, clopidogrel (75 mg once a day) will be used. If the patient has already been prescribed Clopidogrel before the aortic valve intervention e.g. due to apoplexia, the patient will continue this medication following the procedure as an antiplatelet treatment, which is administered according to current guidelines. |
|
|
| Clopidogrel | Drug | Antiplatelets decrease platelet aggregation and inhibit thrombus formation. In NOTION-4 acetylsalicylic acid (75 mg once a day) is used as first line choice. For participants who are allergic to acetylsalicylic acid, clopidogrel (75 mg once a day) will be used. If the patient has already been prescribed Clopidogrel before the aortic valve intervention e.g. due to apoplexia, the patient will continue this medication following the procedure as an antiplatelet treatment, which is administered according to current guidelines. |
|
|
| Edoxaban | Drug | Direct oral anticoagulants (DOAC) treatment will encompass any of the approved drugs: Rivaroxaban, Edoxaban, Dabigatranetexilat, and Apixaban (Table 1). The DOAC dosage will be adjusted according to kidney function (Table 1) and may be adjusted during the study period according to potential changes in guideline recommendations or if new-onset AF would occur in the follow-up period. The specific DOAC prescribed will be determined by the treating physician. If the patient has already been prescribed Marevan before the aortic valve intervention, the patient will continue this medication following the procedure as an oral anticoagulant treatment, which is administered according to current guidelines. |
|
|
| Dabigatran | Drug | Direct oral anticoagulants (DOAC) treatment will encompass any of the approved drugs: Rivaroxaban, Edoxaban, Dabigatranetexilat, and Apixaban (Table 1). The DOAC dosage will be adjusted according to kidney function (Table 1) and may be adjusted during the study period according to potential changes in guideline recommendations or if new-onset AF would occur in the follow-up period. The specific DOAC prescribed will be determined by the treating physician. If the patient has already been prescribed Marevan before the aortic valve intervention, the patient will continue this medication following the procedure as an oral anticoagulant treatment, which is administered according to current guidelines. |
|
|
| Apixaban | Drug | Direct oral anticoagulants (DOAC) treatment will encompass any of the approved drugs: Rivaroxaban, Edoxaban, Dabigatranetexilat, and Apixaban (Table 1). The DOAC dosage will be adjusted according to kidney function (Table 1) and may be adjusted during the study period according to potential changes in guideline recommendations or if new-onset AF would occur in the follow-up period. The specific DOAC prescribed will be determined by the treating physician. If the patient has already been prescribed Marevan before the aortic valve intervention, the patient will continue this medication following the procedure as an oral anticoagulant treatment, which is administered according to current guidelines. |
|
|
| Warfarin | Drug | If the patient has already been prescribed Marevan before the aortic valve intervention, the patient will continue this medication following the procedure as an oral anticoagulant treatment, which is administered according to current guidelines. |
|
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The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT. |
| At 3 months, 1 year and 5 years after TAVI |
| HALT on leaflets | Number of prosthetic leaflets with HALT at CT-scan. | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with ischemic stroke | The clinical endpoint of ischemic stroke verified by cerebrovascular imaging after the TAVI-procedure in patients with vs. without HALT. | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with stroke | Both ischemic and hemorrhagic strokes are included. | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with all-cause death | All cause mortality | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with cardiovascular mortality | Cardiovascular mortality as defined in current VARC definition | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with bleeding | Major bleeding or life-threatening bleeding | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with re-intervention | valve-in-valve TAVI, paravalvular leak closure, SAVR | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with aortic bioprosthetic dysfunction | According to EAPCI/ESC/EACTS definitions | At 3 months, 1 year and 5 years after TAVI |
| Number of participants with bioprosthetic valve failure | Rate of failure according to EAPCI/ESC/EACTS definitions including Rate of valve-related deaths, re-intervention, severe hemodynamic SVD | At 3 months, 1 year and 5 years after TAVI |
| NYHA classification | Assessing NYHA classification over time after TAVI | At 3 months, 1 year and 5 years after TAVI |
| Quality of life scores with 5-level EQ-5D version (EQ5D-5L) | Assessing changes of quality of life scores after TAVI with 5-level EQ-5D version (EQ5D-5L) where lower scores mean better outcome (score from 1 to 5). | At 3 months, 1 year and 5 years after TAVI |
| Quality of life scores with EQ Visual Analogue Scale (EQ VAS) | The EQ Visual Analogue Scale (EQ VAS) has minimum score 0 and maximum score 100, where higher scores mean better outcome. | At 3 months, 1 year and 5 years after TAVI |
| Copenhagen |
| 2100 |
| Denmark |
| D010078 |
| Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D011725 | Pyridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D001562 | Benzimidazoles |
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |