Aortic Valve DiseasePhase 4NCT04437303
Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI)
A Phase 4 study testing Continuation of oral anticoagulants and Interruption of oral anticoagulants in people with Aortic Valve Disease and Aortic Valve Stenosis, run by St. Antonius Hospital at 22 sites in 6 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Disease, Aortic Valve Stenosis, Stroke
- What is being tested?
- Continuation of oral anticoagulants and Interruption of oral anticoagulants
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 858 participants
- Where
- 22 sitesin 6 countries
- Study dates
- 25 Nov 2020to 22 May 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Planned transfemoral or transsubclavian transcatheter aortic valve implantation procedure
- Uses oral anticoagulation at screening
- Provided written informed consent
Who cannot join
- 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
Trial locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
Netherlands11 sites
Amsterdam UMC
Amsterdam
Amphia Hospital
Breda
UMC Groningen
Groningen
Leiden University Medical Center
Leiden
Maastricht UMC+
Maastricht
St. Antonius Ziekenhuis
Nieuwegein, Utrecht, 3435CM
Radboud UMC
Nijmegen
Erasmus MC
Rotterdam
Haga Hospital
The Hague
UMC Utrecht
Utrecht
Isala
Zwolle
Belgium7 sites
A.S.Z. Hospital
Aalst
O.L.V. Hospital
Aalst
ZNA Middelheim
Antwerp
AZ Sint-Jan
Bruges
East Limburg Hospital
Genk
University Hospital Leuven
Leuven
AZ Delta
Roeselare, 8800
Luxembourg1 site
National Institute of Cardiac Surgery and Interventional Cardiology
Luxembourg
About this study
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
- Conditions
- Aortic Valve Disease, Aortic Valve Stenosis, Stroke, Bleeding, Vascular Complications, Myocardial Infarction
- Being tested
- Continuation of oral anticoagulants, Interruption of oral anticoagulants
- Keywords
- 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
- Medical subject headings
- Aortic Valve Disease, Aortic Valve Stenosis, Stroke, Hemorrhage, Myocardial Infarction, Embolism and Thrombosis, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuation of oral anticoagulantsDrug
Oral anticoagulant treatment will not be interrupted before the procedure.
Interruption of oral anticoagulantsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Continuation of oral anticoagulants | Active comparator | Not described Receives: Drug: Continuation of oral anticoagulants |
| Interruption of oral anticoagulants | Active comparator | Not described Receives: Drug: Interruption of oral anticoagulants |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 30 days
Secondary outcomes (13)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 30 days
Neurologic events
Overt CNS injury, covert CNS injury, neurologic dysfunction (acutely symptomatic) without CNS injury as defined by the VARC-3 criteria
Measured: 30 days
Cerebrovascular events
All stroke and TIA as defined by the VARC-3 criteria.
Measured: 30 days
Stroke
All stroke as defined by the VARC-3 criteria
Measured: 30 days
Bleeding complications
Type 1-4 bleeding as defined by the VARC-3 criteria
Measured: 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
Measured: 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
Measured: 30 days
All-cause death
Measured: 30 days
Cardiovascular death
Measured: 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)
Measured: 30 days and 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start25 Nov 2020
- Primary completion21 Mar 2024
- Study completion22 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 858 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Antonius Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jurriën M. ten Berg, MD, PhD, St. Antonius Hospital
- Investigators
- Jurriën M ten Berg, MD PhD, Principal investigator, St. Antonius Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04437303
- Sponsor's protocol ID
- NL73805.100.20
- Status last verified
- May 2024
- First submitted
- 19 May 2020
- Last updated
- 31 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
van Bergeijk KH, Overduin DC, Venema CS, van Ginkel DJ, van der Werf HW, van den Heuvel AFM, Voors AA, Wykrzykowska JJ, Ten Berg JM. Sex Differences in Transcatheter Aortic Valve Implantation Outcomes in Patients on Oral Anticoagulants: A Popular PAUSE TAVI SubAnalysis. J Am Heart Assoc. 2025 Nov 4;14(21):e043448. doi: 10.1161/JAHA.125.043448. Epub 2025 Oct 23.
PubMed 41128170van Ginkel DJ, Bor WL, Aarts HM, Dubois C, De Backer O, Rooijakkers MJP, Rosseel L, Veenstra L, van der Kley F, van Bergeijk KH, Van Mieghem NM, Agostoni P, Voskuil M, Schotborgh CE, IJsselmuiden AJJ, Van Der Heyden JAS, Hermanides RS, Barbato E, Mylotte D, Fabris E, Frambach P, Dujardin K, Ferdinande B, Peper J, Rensing BJWM, Timmers L, Swaans MJ, Brouwer J, Nijenhuis VJ, Overduin DC, Adriaenssens T, Kobari Y, Vriesendorp PA, Montero-Cabezas JM, El Jattari H, Halim J, Van den Branden BJL, Leonora R, Vanderheyden M, Lauterbach M, Wykrzykowska JJ, van 't Hof AWJ, van Royen N, Tijssen JGP, Delewi R, Ten Berg JM; POPular PAUSE TAVI Investigators.; POPular PAUSE TAVI Investigators. Continuation versus Interruption of Oral Anticoagulation during TAVI. N Engl J Med. 2025 Jan 30;392(5):438-449. doi: 10.1056/NEJMoa2407794. Epub 2024 Aug 31.
PubMed 39216096
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI)
- ClinicalTrials.gov ID
- NCT04437303
- Acronym / sponsor ID
- NL73805.100.20
- Conditions
- Aortic Valve Disease, Aortic Valve Stenosis, Stroke, Bleeding, Vascular Complications, Myocardial Infarction
- Keywords
- Transcatheter Aortic Valve Implantation (TAVI), Transcatheter Aortic Valve Replacement (TAVR), Aortic Valve Disease, Aortic Valve Stenosis, Stroke, Bleeding, Vascular Complications, Myocardial Infarction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 858 participants (actual)
- Lead sponsor
- St. Antonius HospitalUniversity, hospital or other
- Study start
- 25 Nov 2020 (actual)
- Primary completion
- 21 Mar 2024 (actual)
- Study completion
- 22 May 2024 (actual)
- First posted
- 18 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuation of oral anticoagulants | Active comparator | Drug: Continuation of oral anticoagulants |
| Interruption of oral anticoagulants | Active comparator | Drug: Interruption of oral anticoagulants |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Planned transfemoral or transsubclavian transcatheter aortic valve implantation procedure
- Uses oral anticoagulation at screening
- Provided written informed consent
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuation of oral anticoagulantsOral anticoagulant treatment will not be interrupted before the procedure. | Drug | Continuation of oral anticoagulants |
| Interruption of oral anticoagulantsPeri-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. | Drug | Interruption of oral anticoagulants |
Primary outcome
Net adverse clinical events
Time frame: 30 days
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
13 secondary outcomes
Procedure related primary endpoints
Time frame: 30 days
Procedure related bleeding complications
Time frame: 30 days
Procedure related thromboembolic complications
Time frame: 30 days
Thromboembolic complications
Time frame: 30 days
Neurologic events
Time frame: 30 days
Cerebrovascular events
Time frame: 30 days
Stroke
Time frame: 30 days
Bleeding complications
Time frame: 30 days
Early safety
Time frame: 30 days
Clinical efficacy
Time frame: 30 days
All-cause death
Time frame: 30 days
Cardiovascular death
Time frame: 30 days
Quality of Life
Time frame: 30 days and 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2024.
- Derived from this study: PubMed 41128170van Bergeijk KH, Overduin DC, Venema CS, van Ginkel DJ, van der Werf HW, van den Heuvel AFM, Voors AA, Wykrzykowska JJ, Ten Berg JM. Sex Differences in Transcatheter Aortic Valve Implantation Outcomes in Patients on Oral Anticoagulants: A Popular PAUSE TAVI SubAnalysis. J Am Heart Assoc. 2025 Nov 4;14(21):e043448. doi: 10.1161/JAHA.125.043448. Epub 2025 Oct 23.
- Derived from this study: PubMed 39216096van Ginkel DJ, Bor WL, Aarts HM, Dubois C, De Backer O, Rooijakkers MJP, Rosseel L, Veenstra L, van der Kley F, van Bergeijk KH, Van Mieghem NM, Agostoni P, Voskuil M, Schotborgh CE, IJsselmuiden AJJ, Van Der Heyden JAS, Hermanides RS, Barbato E, Mylotte D, Fabris E, Frambach P, Dujardin K, Ferdinande B, Peper J, Rensing BJWM, Timmers L, Swaans MJ, Brouwer J, Nijenhuis VJ, Overduin DC, Adriaenssens T, Kobari Y, Vriesendorp PA, Montero-Cabezas JM, El Jattari H, Halim J, Van den Branden BJL, Leonora R, Vanderheyden M, Lauterbach M, Wykrzykowska JJ, van 't Hof AWJ, van Royen N, Tijssen JGP, Delewi R, Ten Berg JM; POPular PAUSE TAVI Investigators.; POPular PAUSE TAVI Investigators. Continuation versus Interruption of Oral Anticoagulation during TAVI. N Engl J Med. 2025 Jan 30;392(5):438-449. doi: 10.1056/NEJMoa2407794. Epub 2024 Aug 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jurriën M ten Berg, MD PhD principal investigator
St. Antonius Hospital
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continuation of oral anticoagulants and Interruption of oral anticoagulants in people with Aortic Valve Disease and Aortic Valve Stenosis, run by St. Antonius Hospital at 22 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Netherlands, Belgium, Denmark, Ireland, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Net adverse clinical events (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04437303, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2024.