Von Willebrand Factor Point-of-care Testing to Improve Minimally Invasive TAVI Outcomes

Study Overview
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Brief Summary
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Paravalvular regurgitation (PVR) is an important complication of Transcatheter Aortic Valve Implantation (TAVI) that is associated with a 2.5-fold increase risk of mortality. Transesophageal echocardiographic (TEE) is considered as the gold standard to assess the severity of PVR and guide the physician to perform corrective procedures during TAVI, but it requires general anesthesia (GA). With such approach (TEE+GA), the PARTNERII trial has demonstrated that very low rate of PVR (3,5%) can be achieved with current devices. Registries have demonstrated a strong trend for using a mini-invasive approach in which the procedure is performed under conscious sedation (CS) without TEE. However, several studies raised concerns on the safety of this mini-invasive approach concerning the PVR rate. Thus, the accurate and real-time assessment of the presence and severity of PVR is an unmet clinical need to optimize TAVI without TEE guidance. A recent study reported that a blood biomarker reflecting the Von Willebrand factor (VWF) activity, i.e. the closure time with adenosine diphosphate (CT-ADP), is a valuable non-invasive, highly reproducible, and easy to perform alternative to TEE for PVR evaluation. The hypothesis is that the measurement of CT-ADP during TAVI performed without TEE guidance can improve both the detection of significant PVR and thus the procedural and clinical outcomes (primary objective).

Official Title
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Point-of-care Haemostasis Testing of Von Willebrand Factor Function Embedded in Catheterization Laboratory to Improve Real-time Management of Paravalvular Regurgitation During Minimally Invasive TAVI

Conditions
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Aortic Valve Stenosis, Aortic Valve Insufficiency

Intervention / Treatment
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* Diagnostic Test: CT-ADP performed during TAVI procedure
* Other: No CT-ADP performed during TAVI procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients scheduled to undergo mini-invasive TAVI at any of the participating centers and fulfilling the inclusion criteria will be eligible for entry in the study. The decision to undertake TAVI will be made by the local heart team. Symptomatic aortic stenosis scheduled to undergo TAVI TAVI performed via mini-invasive approach defined as: transfemoral access route; local anesthesia/conscious sedation; no TEE guidance. All types of prosthetic valves (balloon-expandable, self-expandable, others) are accepted Exclusion Criteria: TAVI through non-transfemoral approach TAVI with concomitant percutaneous coronary intervention TAVI performed under general anesthesia TAVI performed under TEE guidance Valve-in-valve procedure Inability to provide informed consent Associated ≥ moderate mitral regurgitation Peri-procedural treatment with ticagrelor or prasugrel treatment / direct oral anticoagulant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter open-label randomized controlled clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT-ADP group<br>PVR assessment with the standard methods and with the CT-ADP that will be provided to the operator in real-time during TAVI. The decision to undertake corrective procedure will be left at the discretion of the operator and based on the results of the CT-ADP on top of the standard methods of PVR assessment. | Diagnostic Test: CT-ADP performed during TAVI procedure<br>* The CT-ADP will be performed in the catheterization laboratory and revealed to the operator. The decision to undertake corrective procedure will be based on CT-ADP on top of standard methods of PVR assessment.<br>|
| Other: Control group<br>PVR assessment with standard methods only (at discretion of the operator excluding CT-ADP and transesophageal echocardiography). CT-ADP will not be provided to the operator at the time of TAVI. The decision to undertake corrective procedure will be left at the discretion of the operator according to the results of the standard methods of PVR assessment. | Other: No CT-ADP performed during TAVI procedure<br>* PVR assessment with the standard methods only (TTE and/or angiography and/or hemodynamics but excluding TEE and CT-ADP). The decision to undertake corrective procedure will be left at the discretion of the operator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite 1-year event rate of | rate of All-cause death; rate of Paravalvular regurgitation ≥ moderate; rate of Rehospitalization; rate of Stroke; rate of Delayed valve re-intervention; rate of Mean transaortic gradient >20mmHg. | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death rate | All-cause death | At 30 days, at 1 year | 
| PVR rate | PVR superior or egal to moderate | At 30 days, at 1 year | 
| Rehospitalization for heart failure rate | Rehospitalization for heart failure | At 30 days, at 1 year | 
| Delayed valve re-intervention rate | Delayed valve re-intervention | At 1 year | 
| Delayed valve re-intervention rate | Delayed valve re-intervention | At 30 days, at 1 year | 
| Mean transaortic gradient >20mmHg rate | Mean transaortic gradient >20mmHg | At 30 days | 
| composite event rate | All-cause death; PVR superior or egal to moderate; Rehospitalization for heart failure; All stroke (transient or definite); Delayed valve re-intervention; Mean transaortic gradient >20mmHg | At 30 days | 
| composite event rate of the following individual safety endpoints | Aortic injury; Coronary artery occlusion; Tamponade; All stroke (transient or definite) | at 24hours | 
| Aortic injury rate | Aortic injury | at 24hours | 
| Coronary artery occlusion rate | Coronary artery occlusion | at 24hours | 
| Tamponade rate | Tamponade | at 24hours | 
| All stroke (transient or definite) rate | All stroke (transient or definite) | at 24hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter Aortic Valve Replacement, Paravalvular regurgitation, Point-of-care test, Biomarker, Aortic stenosis, Von willebrand Factor