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Active, Not Recruiting

NCT Number: NCT06449469

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Aarhus University Hospital, Skejby, Aarhus, Denmark

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: SUB29263

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.

Other names: SUB12730MIG

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.

Other names: SUB13395MIG

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.

Other names: SUB32701

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.

Other names: SUB20521

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.

Other names: SUB25425

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.

Other names: SUB05128MIG

Primary outcomes

  1. HALT after 1 year

    Time frame: At 1 year after TAVI

    The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT at one year after TAVI.

Secondary outcomes

  1. 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

    Combined clinical endpoint of all-cause mortality, thromboembolic event, and life-threatening or major bleeding

  2. Incidence of patients with HALT during follow up

    Time frame: At 3 months, 1 year and 5 years after TAVI

    The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT.

  3. HALT on leaflets

    Time frame: At 3 months, 1 year and 5 years after TAVI

    Number of prosthetic leaflets with HALT at CT-scan.

  4. Number of participants with ischemic stroke

    Time frame: At 3 months, 1 year and 5 years after TAVI

    The clinical endpoint of ischemic stroke verified by cerebrovascular imaging after the TAVI-procedure in patients with vs. without HALT.

  5. Number of participants with stroke

    Time frame: At 3 months, 1 year and 5 years after TAVI

    Both ischemic and hemorrhagic strokes are included.

  6. Number of participants with all-cause death

    Time frame: At 3 months, 1 year and 5 years after TAVI

    All cause mortality

  7. Number of participants with cardiovascular mortality

    Time frame: At 3 months, 1 year and 5 years after TAVI

    Cardiovascular mortality as defined in current VARC definition

  8. Number of participants with bleeding

    Time frame: At 3 months, 1 year and 5 years after TAVI

    Major bleeding or life-threatening bleeding

  9. Number of participants with re-intervention

    Time frame: At 3 months, 1 year and 5 years after TAVI

    valve-in-valve TAVI, paravalvular leak closure, SAVR

  10. Number of participants with aortic bioprosthetic dysfunction

    Time frame: At 3 months, 1 year and 5 years after TAVI

    According to EAPCI/ESC/EACTS definitions

  11. Number of participants with bioprosthetic valve failure

    Time frame: At 3 months, 1 year and 5 years after TAVI

    Rate of failure according to EAPCI/ESC/EACTS definitions including Rate of valve-related deaths, re-intervention, severe hemodynamic SVD

  12. NYHA classification

    Time frame: At 3 months, 1 year and 5 years after TAVI

    Assessing NYHA classification over time after TAVI

  13. Quality of life scores with 5-level EQ-5D version (EQ5D-5L)

    Time frame: At 3 months, 1 year and 5 years after TAVI

    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).

  14. Quality of life scores with EQ Visual Analogue Scale (EQ VAS)

    Time frame: At 3 months, 1 year and 5 years after TAVI

    The EQ Visual Analogue Scale (EQ VAS) has minimum score 0 and maximum score 100, where higher scores mean better outcome.

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Collaborators

  • Aarhus University Hospital Skejby

Registry information

Official study 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)

Acronym: NOTION-4

Important dates

Study start
2021
Primary completion
2026
Study completion
2030
First posted
Jun 10, 2024
Registry last updated
Apr 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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