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

Prospective study on the impact of different anti-thrombotic therapies on subclinical leaflet thickening and its temporal dynamics in transcatheter bioprosthetic aortic valves The Nordic Aortic Valve Intervention Trial 4 (NOTION-4) - NOTION-4

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-003361-19-DK

Enrollment

324

Registered

2020-08-11

Start date

2020-09-07

Completion date

Unknown

Last updated

2024-04-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients who have undergone successful transcatheter bioprosthetic aortic valve implantation (TAVI) MedDRA version: 20.0 Level: LLT Classification code 10077017 Term: TAVI System Organ Class: 10042613 - Surgical and medical procedures

Interventions

Pharmaceutical Form: Tablet INN or Proposed INN: ACETYLSALICYLIC ACID Current Sponsor code: ACETYLSALICYLIC ACID Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 75-

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Patients who underwent successful TAVI according to Valve Academic Research Consortium (VARC)-2 criteria Residing in Denmark Provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 292

Exclusion criteria

Exclusion criteria: Atrial fibrillation or any other indication for lifelong OAC 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

Design outcomes

Primary

Measure	Time frame
Main Objective: The objective of NOTION-4 is to investigate the incidence and temporal dynamics of subclinical leaflet thickening (HALT) by cardiac CT in transcatheter bioprosthetic aortic valves in patients randomised to different anti-thrombotic strategies. ;Secondary Objective: Additionally, this study aims to examine a possible association between HALT and thromboembolic events.;Primary end point(s): The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT at one year after TAVI.;Timepoint(s) of evaluation of this end point: One year after TAVI.	—

Measure

Time frame

Main Objective: The objective of NOTION-4 is to investigate the incidence and temporal dynamics of subclinical leaflet thickening (HALT) by cardiac CT in transcatheter bioprosthetic aortic valves in patients randomised to different anti-thrombotic strategies. ;Secondary Objective: Additionally, this study aims to examine a possible association between HALT and thromboembolic events.;Primary end point(s): The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT at one year after TAVI.;Timepoint(s) of evaluation of this end point: One year after TAVI.

—

Secondary

Measure	Time frame
Secondary end point(s): 1) The combined clinical endpoint of all-cause mortality, thromboembolic event, and life-threatening or major bleeding at 1 year, 3 years and 5 years after randomization 2) The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT at 3 months, 1, 3 and 5 years after TAVI 3) Number of prosthetic leaflets with HALT at CT-scan at 3 months, 1 year, 3 and 5 years. 4) The clinical endpoint of ischemic stroke verified by cerebrovascular imaging after the TAVI-procedure in patients with vs. without HALT. 5) Any type of stroke – including ischemic and hemorrhagic stroke 6) All-cause mortality 7) Cardiovascular mortality as defined in current VARC definition 8) Major bleeding or life-threatening bleeding 9) Need for re-intervention (valve-in-valve TAVI, paravalvular leak closure, SAVR) 10) Aortic bioprosthetic dysfunction (according to EAPCI/ESC/EACTS definitions) (13) a) Structural valve deterioration (SVD) i) Moderate hemodynamic SVD (1) Mean transprosthetic gradient =20mmHg and 1+/4+) from baseline ii) Severe hemodynamic SVD (1) Mean transprosthetic gradient =40mmHg (2) Mean transprosthetic gradient =20mmHg change from baseline (3) Severe intra-prosthetic aortic regurgitation, new or worsening (>2+/4+) from baseline iii) Morphological SVD (any of the following) (1) Leaflet integrity abnormality; Leaflet structure abnormality; Leaflet function abnormality; Strut/frame abnormality iv) Haemodynamic and morphological SVD b) Nonstructural valve deterioration i) Intra-prosthetic, paravalvular regurgitation, prosthesis malposition, patient-prosthesis mismatch or late embolization that occurred within three months after AVR c) Thrombus development on any structure of the prosthetic valve, leading to dysfunction with or without thromboembolism d) Endocarditis involving any structure of the prosthetic aortic valve 11) Rate of bioprosthetic valve failure (according to EAPCI/ESC/EACTS definitions) a) Rate of valve-	—

Measure

Time frame

Secondary end point(s): 1) The combined clinical endpoint of all-cause mortality, thromboembolic event, and life-threatening or major bleeding at 1 year, 3 years and 5 years after randomization 2) The number of patients with at least one prosthetic valve leaflet with HALT as assessed by cardiac CT at 3 months, 1, 3 and 5 years after TAVI 3) Number of prosthetic leaflets with HALT at CT-scan at 3 months, 1 year, 3 and 5 years. 4) The clinical endpoint of ischemic stroke verified by cerebrovascular imaging after the TAVI-procedure in patients with vs. without HALT. 5) Any type of stroke – including ischemic and hemorrhagic stroke 6) All-cause mortality 7) Cardiovascular mortality as defined in current VARC definition 8) Major bleeding or life-threatening bleeding 9) Need for re-intervention (valve-in-valve TAVI, paravalvular leak closure, SAVR) 10) Aortic bioprosthetic dysfunction (according to EAPCI/ESC/EACTS definitions) (13) a) Structural valve deterioration (SVD) i) Moderate hemodynamic SVD (1) Mean transprosthetic gradient =20mmHg and 1+/4+) from baseline ii) Severe hemodynamic SVD (1) Mean transprosthetic gradient =40mmHg (2) Mean transprosthetic gradient =20mmHg change from baseline (3) Severe intra-prosthetic aortic regurgitation, new or worsening (>2+/4+) from baseline iii) Morphological SVD (any of the following) (1) Leaflet integrity abnormality; Leaflet structure abnormality; Leaflet function abnormality; Strut/frame abnormality iv) Haemodynamic and morphological SVD b) Nonstructural valve deterioration i) Intra-prosthetic, paravalvular regurgitation, prosthesis malposition, patient-prosthesis mismatch or late embolization that occurred within three months after AVR c) Thrombus development on any structure of the prosthetic valve, leading to dysfunction with or without thromboembolism d) Endocarditis involving any structure of the prosthetic aortic valve 11) Rate of bioprosthetic valve failure (according to EAPCI/ESC/EACTS definitions) a) Rate of valve-

—

Countries

Denmark

Contacts

Public ContactOle de Backer

Rigshospitalet

ole.de.backer@regionh.dk004535457086

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026