The Nordic Aortic Valve Intervention Trial 4 (NOTION-4)

Cardiovascular Diseases Clinical Trial

— NOTION-4  

Official title:

Prospective Study on the Impact of Different Anti-thrombotic Therapies on Subclinical Leaflet Thickening and Its Temporal Dynamics in Transcatheter Bioprosthetic Aortic Valves (NOTION-4)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06449469
• Other study ID #: 2020-003361-19
• Secondary ID: 2020-003361-19
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2021
• Est. completion date: January 1, 2029

Study information

• Verified date: June 2024
• Source: Rigshospitalet, Denmark
• Contact: Jani Thuraiaiyah, MD
• Phone: 35456342
• Email: jani.thuraiaiyah[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 324
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients who underwent successful TAVI according to Valve Academic Research Consortium (VARC)-2 criteria

• Residing in Denmark

• Provided written informed consent

Exclusion Criteria:

• Atrial fibrillation or any other indication for lifelong oral anticoagulant therapy

• Patient deemed not suitable for DOAC treatment because of previous life-threatening or major bleeding, e.g. intracranial haemorrhage or major gastrointestinal bleeding

• Patients with severe renal insufficiency (eGFR <30 mL/min/1.73 m2)

• Patient with absolute indication for anti-thrombotic therapy, e.g. recent PCI

• Iodine contrast allergy or other condition that prohibits CT imaging

• Age <18 years

• Women of childbearing potential, pregnant or nursing

Related Conditions & MeSH terms

• Aortic Diseases
• Aortic Valve Disease
• Aortic Valve Stenosis
• Cardiovascular Diseases
• Heart Diseases
• Heart Valve Diseases

Intervention

Drug:
• Rivaroxaban
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.
• Acetylsalicylic acid
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
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
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
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
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.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Skejby	Aarhus
Denmark	Rigshospitalet	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Aarhus University Hospital Skejby

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Combined clinical endpoint of all-cause mortality, thromboembolic event, and life-threatening or major bleeding		At 3 months, 12 months, and then yearly up to 5 years after TAVI
Secondary	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.	At 3 months, 1 year and 5 years after TAVI
Secondary	HALT on leaflets	Number of prosthetic leaflets with HALT at CT-scan.	At 3 months, 1 year and 5 years after TAVI
Secondary	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 then yearly up to 5 years after TAVI
Secondary	Number of participants with stroke	Both ischemic and hemorrhagic strokes are included.	At 3 months, 12 months, and then yearly up to 5 years after TAVI
Secondary	Number of participants with all-cause death	All cause mortality	At 3 months, 12 months, and then yearly up to 5 years after TAVI
Secondary	Number of participants with cardiovascular mortality	Cardiovascular mortality as defined in current VARC definition	At 3 months, 12 months, and then yearly up to 5 years after TAVI
Secondary	Number of participants with bleeding	Major bleeding or life-threatening bleeding	At 3 months, 12 months, and then yearly up to 5 years after TAVI
Secondary	Number of participants with re-intervention	valve-in-valve TAVI, paravalvular leak closure, SAVR	At 3 months, 12 months, and then yearly up to 5 years after TAVI
Secondary	Number of participants with aortic bioprosthetic dysfunction	According to EAPCI/ESC/EACTS definitions	At 3 months, 1 year and 5 years after TAVI
Secondary	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, 3 years and 5 years after TAVI
Secondary	NYHA classification	Assessing NYHA classification over time after TAVI	At 3 months, 1 year and 5 years after TAVI
Secondary	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, 3 years and 5 years after TAVI
Secondary	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, 3 years and 5 years after TAVI