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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Myocardial Infarction; Stroke; Bleeding; Aortic Valve Stenosis; Aortic Valve Disease; Thrombosis Embolism; Vascular Complications
• Intervention / Treatment: Drug: Continuation of oral anticoagulants; Drug: Interruption of oral anticoagulants

• Study Type: Interventional
• Enrollment (Actual): 858
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wilbert Bor, MD; Phone Number: +31 (0)88 320 12 41; Email: w.bor@antoniusziekenhuis.nl
• Study Contact Backup: Name: Dirk-Jan van Ginkel, MD; Phone Number: +31 (0)88 320 66 48; Email: d.van.ginkel@antoniusziekenhuis.nl

Study Locations

• Belgium
  • Aalst, Belgium
    • A.S.Z. Hospital
  • Aalst, Belgium
    • O.L.V. Hospital
  • Antwerp, Belgium
    • ZNA Middelheim
  • Brugge, Belgium
    • AZ Sint-Jan
  • Genk, Belgium
    • East Limburg Hospital
  • Leuven, Belgium
    • University Hospital Leuven
  • Roeselare, Belgium, 8800
    • AZ Delta
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet Copenhagen
• Ireland
  • Galway, Ireland
    • University Hospital Galway
• Italy
  • Trieste, Italy
    • Azienda Sanitaria Universitaria Integrata di Trieste
• Luxembourg
  • Luxembourg, Luxembourg
    • National Institute of Cardiac Surgery and Interventional Cardiology
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
  • Breda, Netherlands
    • Amphia Hospital
  • Groningen, Netherlands
    • UMC Groningen
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Maastricht, Netherlands
    • Maastricht UMC+
  • Nijmegen, Netherlands
    • Radboud UMC
  • Rotterdam, Netherlands
    • Erasmus MC
  • The Hague, Netherlands
    • Haga Hospital
  • Utrecht, Netherlands
    • UMC Utrecht
  • Zwolle, Netherlands
    • Isala
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435CM
      • St. Antonius Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuation of oral anticoagulants	Drug: Continuation of oral anticoagulants; Oral anticoagulant treatment will not be interrupted before the procedure.
Active Comparator: Interruption of oral anticoagulants	Drug: Interruption of oral anticoagulants; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net adverse clinical events	A composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding complications at 30 days post TAVI as defined by the VARC-3 criteria	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death		30 days
Procedure related primary endpoints	Cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding complications as defined by the VARC-3 criteria considered procedure related as adjudicated by the clinical event committee	30 days
Procedure related bleeding complications	Type 1-4 bleeding as defined by the VARC-3 criteria considered procedure related as adjudicated by the clinical event committee	30 days
Procedure related thromboembolic complications	All stroke (except haemorrhagic), TIA, myocardial infarction, systemic embolism (vascular complications: distal embolization (non-cerebral) from a vascular source) as defined by the VARC-3 criteria considered procedure related as adjudicated by the clinical event committee	30 days
Thromboembolic complications	All stroke (except haemorrhagic), TIA, myocardial infarction and systemic embolism (vascular complications: distal embolization (non-cerebral) from a vascular source) as defined by the VARC-3 criteria	30 days
Neurologic events	Overt CNS injury, covert CNS injury, neurologic dysfunction (acutely symptomatic) without CNS injury as defined by the VARC-3 criteria	30 days
Cerebrovascular events	All stroke and TIA as defined by the VARC-3 criteria.	30 days
Stroke	All stroke as defined by the VARC-3 criteria	30 days
Bleeding complications	Type 1-4 bleeding as defined by the VARC-3 criteria	30 days
Early safety	Freedom from all-cause mortality, all stroke, VARC type 2-4 bleeding, major vascular, access-related, or cardiac structural complication, acute kidney injury stage 3 or 4, moderate or severe aortic regurgitation, new permanent pacemaker due to procedure related conduction abnormalities, surgery or intervention related to the device as defined by the VARC-3 criteria	30 days
Clinical efficacy	Freedom from: all-cause mortality, all stroke, hospitalization for procedure- or valve-related causes, KCCQ Overall Summary Score <45 or decline from baseline of >10 point as defined by the VARC-3 criteria	30 days
Cardiovascular death		30 days
Quality of Life	Assessed by Short Form(SF)-12, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Toronto aortic stenosis quality of life questionnaire (TASQ)	30 days and 90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
New York Heart Association class for heart failure		30 days
Rehospitalisation		30 days
Permanent pacemaker implantation		30 days
Bleeding	As classified by Bleeding Academic Research Consortium (BARC) criteria	30 days

Collaborators and Investigators

• Sponsor: St. Antonius Hospital
• Investigators: Principal Investigator: Jurriën M ten Berg, MD PhD, St. Antonius Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): March 21, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Stroke; Protamine; Warfarin; Bleeding; Aortic Valve Stenosis; Myocardial Infarction; Vitamin K Antagonist; Heart Diseases; Aortic Valve Disease; Transcatheter Aortic Valve Implantation (TAVI); Transcatheter Aortic Valve Replacement (TAVR); Oral Anticoagulation; Vascular Complications; Thrombosis Embolism; Direct Acting Oral Anticoagulants
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Myocardial Infarction; Infarction; Embolism; Aortic Valve Stenosis; Thrombosis; Aortic Valve Disease; Embolism and Thrombosis; Anticoagulants
• Other Study ID Numbers: NL73805.100.20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No