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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
352
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.
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.
Aarhus University Hospital, Skejby
Aarhus, Denmark
Rigshospitalet
Copenhagen, Denmark
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.
Time frame: At 1 year after TAVI
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
Time frame: At 1 year and 5 years after TAVI
Incidence of patients with HALT during follow up
The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT.
Time frame: At 3 months, 1 year and 5 years after TAVI
HALT on leaflets
Number of prosthetic leaflets with HALT at CT-scan.
Time frame: 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.
Time frame: At 3 months, 1 year and 5 years after TAVI
Number of participants with stroke
Both ischemic and hemorrhagic strokes are included.
Time frame: At 3 months, 1 year and 5 years after TAVI
Number of participants with all-cause death
All cause mortality
Time frame: At 3 months, 1 year and 5 years after TAVI
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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.
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.
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.
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.
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.
Number of participants with cardiovascular mortality
Cardiovascular mortality as defined in current VARC definition
Time frame: At 3 months, 1 year and 5 years after TAVI
Number of participants with bleeding
Major bleeding or life-threatening bleeding
Time frame: At 3 months, 1 year and 5 years after TAVI
Number of participants with re-intervention
valve-in-valve TAVI, paravalvular leak closure, SAVR
Time frame: At 3 months, 1 year and 5 years after TAVI
Number of participants with aortic bioprosthetic dysfunction
According to EAPCI/ESC/EACTS definitions
Time frame: 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
Time frame: At 3 months, 1 year and 5 years after TAVI
NYHA classification
Assessing NYHA classification over time after TAVI
Time frame: 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).
Time frame: 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.
Time frame: At 3 months, 1 year and 5 years after TAVI