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

NCT06449469 | Active Not Recruiting DMC

• 1 other identifier: 2020-003361-19
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Aortic Valve Stenosis; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Valve Disease, Aortic

Keywords

heart valve disease; valvular bioprosthesis; aortic valve replacement; Randomized clinical trial; TAVI; Antitrombotic medication

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• 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

  At 3 months, 1 year and 5 years after TAVI

• HALT on leaflets

  At 3 months, 1 year and 5 years after TAVI

• Number of participants with ischemic stroke

  At 3 months, 1 year and 5 years after TAVI

• Number of participants with stroke

  At 3 months, 1 year and 5 years after TAVI

Study Arms (2)

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.

Drug: Rivaroxaban; Drug: Edoxaban; Drug: Dabigatran; Drug: Apixaban; Drug: Warfarin

Sinus rhythm - Anti-platelet treatment

ACTIVE COMPARATOR

Can be either of the following anti-platelet components: acetylsalicylic acid or clopidogrel. Duration: Lifelong

Drug: Acetylsalicylic acid; Drug: Clopidogrel

Interventions

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.

Also known as: SUB29263

Sinus rhythm - DOAC treatment

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.

Also known as: SUB12730MIG

Sinus rhythm - Anti-platelet treatment

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.

Also known as: SUB13395MIG

Sinus rhythm - Anti-platelet treatment

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.

Also known as: SUB32701

Sinus rhythm - DOAC treatment

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.

Also known as: SUB20521

Sinus rhythm - DOAC treatment

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.

Also known as: SUB25425

Sinus rhythm - DOAC treatment

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.

Also known as: SUB05128MIG

Sinus rhythm - DOAC treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who underwent successful TAVI according to Valve Academic Research Consortium (VARC)-2 criteria
• Residing in Denmark
• Provided written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Aarhus University Hospital Skejby: collaborator

Study Sites (2)

Aarhus University Hospital, Skejby

Aarhus, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (1)

• 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.

  PMID: 39374638 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Aortic Valve Disease

Interventions

Rivaroxaban; Aspirin; Clopidogrel; edoxaban; Dabigatran; apixaban; Warfarin

Condition Hierarchy (Ancestors)

Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzimidazoles; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Officials

• Ole De Backer, PhD

  Rigshospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: June 10, 2024
• Study Start: May 1, 2021
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2030
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)