Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI)

Study Overview
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Brief Summary
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Transcatheter aortic valve implantation (TAVI) is a rapidly growing treatment option for patients with aortic valve stenosis. Stroke is a feared complication of TAVI, with an incidence of around 4-5% in the first 30 days. Up to 50% of patients undergoing TAVI have an indication for oral anticoagulants (OAC) mostly for atrial fibrillation. OAC use during TAVI could increase bleeding complications, but interruption during TAVI may increase the risk for thromboembolic events (i.e. stroke, systemic embolism, myocardial infarction). Recent observational data suggest that periprocedural continuation of OAC is safe and might decrease the risk of stroke. Beside the potential reduction of thromboembolic events, continuation of OAC is associated with an evident clinical ancillary benefit for patients and staff. Since periprocedural OAC interruption not infrequently leads to misunderstanding and potentially dangerous situations, when patients are not properly informed before hospital admission or may experience difficulties with the interruption regimen. Hypothesis: Periprocedural continuation of oral anticoagulants is safe and might decrease thromboembolic complications without an increase in bleeding complications at 30 days

Official Title
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Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI)

Conditions
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Aortic Valve Disease, Aortic Valve Stenosis, Stroke, Bleeding, Vascular Complications, Myocardial Infarction, Thrombosis Embolism

Intervention / Treatment
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* Drug: Continuation of oral anticoagulants
* Drug: Interruption of oral anticoagulants


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Planned transfemoral or transsubclavian transcatheter aortic valve implantation procedure Uses oral anticoagulation at screening Provided written informed consent Exclusion Criteria: Patients at high risk for thromboembolism for whom interruption of oral anticoagulants is no option, i.e.: Mechanical heart valve prosthesis Intracardiac thrombus < 3 months after venous thromboembolism < 6 months after transient ischemic attack or stroke in patients with atrial fibrillation

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Continuation of oral anticoagulants<br> | Drug: Continuation of oral anticoagulants<br>* Oral anticoagulant treatment will not be interrupted before the procedure.<br>|
| Active Comparator: Interruption of oral anticoagulants<br> | Drug: Interruption of oral anticoagulants<br>* Peri-operative interruption of oral anticoagulants will be according to the Dutch guideline on antithrombotic therapy. For direct oral anticoagulant users this will be in general 48 hours before the procedure, except for Dabigatran users with renal insufficiency: with estimated glomerular filtration rate 50-80 mL/min/1.73m^2 72 hours and with estimated glomerular filtration rate 30-50 mL/min/1.73m^2 96 hours before procedure. For vitamin K antagonist users this will be 5 days for phenprocoumon and 3 days for acenocoumarol. After the procedure oral anticoagulants will be resumed after 24 hours, if deemed safe by the treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net clinical benefit | A composite of cardiovascular mortality, stroke, myocardial infarction, major vascular complications and major, disabling and life-threatening bleeding complications at 30 days post TAVI as defined by the VARC-2 criteria. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolic complications | Composite of stroke, transient ischemic attack, systemic embolism, distal embolization, myocardial infarction, and cardiovascular death not caused by bleeding | 30 days | 
| Bleeding and vascular access site complications | Composite of bleeding and vascular access site and access-related complications (except distal embolization and systemic embolism) | 30 days | 
| Early safety as defined by Valve Academic Research Consortium 2 criteria | Composite of all-cause mortality, all stroke, life-threatening bleeding, stage 2 or 3 acute kidney injury, coronary artery obstruction requiring intervention, major vascular complication, and valve-related dysfunction requiring repeat procedure (balloon valvuloplasty or valve replacement) | 30 days | 
| Clinical efficacy as defined by Valve Academic Research Consortium 2 criteria | Composite of all-cause mortality, all stroke, hospitalizations for valve related symptoms or worsening congestive heart failure, New York Heart Association class for heart failure 3/4, and valve-related dysfunction (mean aortic valve gradient >=20 mmHg, effective orifice area (EOA) <=0.9-1.1 cm^2 and/or Doppler velocity index (DVI) <0.35 m/s, AND/OR moderate or severe prosthetic valve regurgitation) | 30 days | 
| All-cause death |  | 30 days | 
| Quality of life assessed by Short Form-12 Questionnaire |  | 3 months | 
| Quality of life assessed by Toronto Aortic Stenosis Questionnaire |  | 3 months | 
| Quality of life assessed by Kansas City Cardiomyopathy Questionnaire |  | 3 months | 
| Stroke |  | 30 days | 
| Stroke and transient ischemic attack |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter Aortic Valve Implantation (TAVI), Transcatheter Aortic Valve Replacement (TAVR), Aortic Valve Disease, Aortic Valve Stenosis, Stroke, Bleeding, Vascular Complications, Myocardial Infarction, Thrombosis Embolism, Heart Diseases, Oral Anticoagulation, Warfarin, Vitamin K Antagonist, Direct Acting Oral Anticoagulants, Protamine