Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
2,600
Countries
5
Sites
33
aortic valve stenosis
To evaluate whether a personalized, CT-guided antithrombotic strategy is superior to standard care lifelong SAPT in reducing the risk of cardiovascular mortality, thromboembolic and bleeding events after TAVI in patients without an existing indication for OAC.
Key facts
- Sponsor
- St Antonius Hospital
- Participant type
- Patients
- Age range
- 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 21 Dec 2023 → ongoing
- Decision date (initial)
- 2025-07-09
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- ZonMw
External identifiers
- EU CT number
- 2023-504637-42-01
- WHO UTN
- U1111-1289-8617
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Dose response, Safety, Therapy, Efficacy
To evaluate whether a personalized, CT-guided antithrombotic strategy is superior to standard care lifelong SAPT in reducing the risk of cardiovascular mortality, thromboembolic and bleeding events after TAVI in patients without an existing indication for OAC.
Secondary objectives 9
- To evaluate the effect of a CT-guided antithrombotic strategy on a net clinical benefit, defined as the composite of cardiovascular mortality, stroke, transient ischaemic attack, systemic embolism, clinically significant valve thrombosis and type 1-4 bleeding according to the VARC-3 criteria.
- To evaluate the effect of a CT-guided antithrombotic strategy on major bleeding (VARC-3 type 2-4)
- To evaluate the effect of a CT-guided antithrombotic strategy on cerebrovascular events (All stroke and TIA according to VARC-3)
- To evaluate the effect of a CT-guided antithrombotic strategy cardiovascular mortality
- To evaluate the effect of a CT-guided antithrombotic strategy on all-cause mortality
- To evaluate the effect of a CT-guided antithrombotic strategy on cerebrovascular events (All stroke and TIA according to VARC-3)
- To evaluate the effect of a CT-guided antithrombotic strategy on quality of life as assessed by EuroQol- 5 Dimension 5 Level (EQ-5D-5L), Kansas City Cardiomyopathy Questionnaire (KCCQ) and Short Form Health Survey (SF-12) at baseline, 3 and 12 months, and then yearly after TAVI procedure.
- To evaluate the effect of a CT-guided antithrombotic strategy on medication adherence as assessed by the Medication Adherence Report Scale (MARS-5) yearly after randomization.
- To evaluate the effect of a CT-guided antithrombotic strategy on cost-effectiveness of a CT-guided antithrombotic strategy after TAVI
Conditions and MedDRA coding
aortic valve stenosis
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-504637-42-00 | Personalized, CT-guided antithrombotic therapy versus lifelong single antiplatelet therapy to reduce thromboembolic and bleeding events in non-atrial fibrillation patients after transcatheter aortic valve implantation: a pragmatic, international, multicentre, randomized clinical trial (POPular ATLANTIS trial) | St Antonius Hospital |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Successful TAVI (according to the VARC-3 criteria) with any approved device
- Ability to understand and to comply with the study protocol
- Written informed consent
Exclusion criteria 2
- Existing indication for oral anticoagulation (e.g. atrial fibrillation, obstructive valve thrombosis detected by echocardiography prior to inclusion)
- Creatinine clearance <30 mL/min (based on the CKD-EPI formula) or on renal replacement therapy
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoints are thromboembolic and bleeding events: Thromboembolic events, defined as the composite of cardiovascular mortality, ischaemic stroke, transient ischaemic attack, myocardial infarction, systemic embolism and clinically significant valve thrombosis according to the VARC-3 criteria. All bleeding, defined as the composite of type 1-4 bleeding, according to the VARC-3 criteria.
Secondary endpoints 9
- Net clinical benefit, defined as the composite of cardiovascular mortality, stroke, transient ischaemic attack, systemic embolism, clinically significant valve thrombosis and type 1-4 bleeding according to the VARC-3 criteria.
- Major bleeding (VARC-3 type 2-4)
- Cerebrovascular events (All stroke and TIA according to VARC-3)
- Cardiovascular mortality
- All-cause mortality
- Aortic bio-prosthetic valve dysfunction assessed by echocardiography yearly after TAVI (standard care).
- Quality of life as assessed by EuroQol- 5 Dimension 5 Level (EQ-5D-5L), Kansas City Cardiomyopathy Questionnaire (KCCQ) and Short Form Health Survey (SF-12) at baseline, 3 and 12 months, and then yearly after TAVI procedure.
- Medication adherence as assessed by the Medication Adherence Report Scale (MARS-5) yearly after randomization.
- To evaluate the cost-effectiveness of a CT-guided antithrombotic strategy after TAVI.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 7
PRD3302213 · Product
- Active substance
- Warfarin Sodium
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AA03 — WARFARIN
- Marketing authorisation
- PA 2050/001/004
- MA holder
- SUN PHARMACEUTICAL INDUSTRIES EUROPE B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
COUMADINE 2 mg, comprimé sécable
PRD8913037 · Product
- Active substance
- Warfarin Sodium
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 99 mg milligram(s)
- Max total dose
- 99 mg milligram(s)
- Max treatment duration
- 9999 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AA03 — WARFARIN
- Marketing authorisation
- 34009 302 645 4 6
- MA holder
- TEOFARMA S.R.L.
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Acenocoumarol Sandoz 1 mg, tabletten
PRD768976 · Product
- Active substance
- Acenocoumarol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AA07 — ACENOCOUMAROL
- Marketing authorisation
- RVG 04464
- MA holder
- SANDOZ B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Eliquis 5 mg film-coated tablets
PRD2351314 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/006
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fenprocoumon Sandoz 3 mg, tabletten
PRD744706 · Product
- Active substance
- Phenprocoumon
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 30 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AA04 — PHENPROCOUMON
- Marketing authorisation
- RVG 21068
- MA holder
- SANDOZ B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Eliquis 2.5 mg film-coated tablets
PRD2351235 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/001
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD3990419 · Product
- Active substance
- Acenocoumarol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 99 mg milligram(s)
- Max total dose
- 99 mg milligram(s)
- Max treatment duration
- 9999 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AA07 — ACENOCOUMAROL
- Marketing authorisation
- 34009 336 628 5 1
- MA holder
- MERUS LABS LUXCO II S.À R.L.
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 5
KARDEGIC 75 mg, poudre pour solution buvable en sachet-dose
PRD432444 · Product
- Active substance
- D,L-Lysine Acetylsalicylate
- Pharmaceutical form
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 75 mg milligram(s)
- Max total dose
- 75 mg milligram(s)
- Max treatment duration
- 9999 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AC06 — ACETYLSALICYLIC ACID
- Marketing authorisation
- 34009 347 441 9 8
- MA holder
- SANOFI WINTHROP INDUSTRIE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Acetylsalicylzuur Cardio Mylan 80 mg, dispergeerbare tabletten
PRD839917 · Product
- Active substance
- Acetylsalicylic Acid
- Substance synonyms
- ASPIRIN, ACETYLSALICYLIC ACID (ASA), ACIDUM ACETYLSALICYLICUM
- Pharmaceutical form
- DISPERSIBLE TABLET
- Route of administration
- ORAL
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 80 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- N02BA01, B01AC06 — ACETYLSALICYLIC ACID, ACETYLSALICYLIC ACID
- Marketing authorisation
- RVG 26194
- MA holder
- MYLAN B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Ticagrelor Mylan 90 mg film-coated tablets
PRD8816453 · Product
- Active substance
- Ticagrelor
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 180 mg milligram(s)
- Max total dose
- 180 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AC24 — -
- Marketing authorisation
- PA0577/235/002
- MA holder
- MCDERMOTT LABORATORIES LTD
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Prasugrel Teva 10 mg Film-coated Tablets
PRD5938263 · Product
- Active substance
- Prasugrel
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AC22 — -
- Marketing authorisation
- PL 00289/2166
- MA holder
- TEVA UK LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Clopidogrel Xiromed 75 mg filmomhulde tabletten
PRD9725701 · Product
- Active substance
- Clopidogrel
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 99 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AC04 — CLOPIDOGREL
- Marketing authorisation
- RVG 127948
- MA holder
- MEDICAL VALLEY INVEST AB
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
St Antonius Hospital
- Sponsor organisation
- St Antonius Hospital
- Address
- Koekoekslaan 1
- City
- Nieuwegein
- Postcode
- 3435 CM
- Country
- Netherlands
Scientific contact point
- Organisation
- St Antonius Hospital
- Contact name
- Christiaan Overduin
Public contact point
- Organisation
- St Antonius Hospital
- Contact name
- Christiaan Overduin
Locations
5 EU/EEA countries · 33 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 300 | 9 |
| Denmark | Ongoing, recruiting | 200 | 1 |
| France | Ongoing, recruiting | 1,300 | 14 |
| Germany | Authorised, recruitment pending | 150 | 1 |
| Netherlands | Ongoing, recruiting | 650 | 8 |
| Rest of world | — | 0 | — |
Investigational sites
Universitair Ziekenhuis Antwerpen
Cardiology, Drie Eikenstraat 655, 2650, Edegem
AZ Delta uw Ziekenhuis Campus Rumbeke, campus Brugsesteenweg Roeselare
Cardiology, AZ Delta Campus, campus Brugsesteenweg, Roselare
AZORG Campus Aalst-Moorselbaan
Cardiology, Moorselbaan 164, 9300, Aalst
Ziekenhuis Oost-Limburg
Cardiology, Schiepse Bos 6, Belgium, Genk
Az Maria Middelares Gent
Cardiology, Buitenring-Sint-Denijs 30, 9000, Gent
Imelda Hospital Bonheiden
Cardiology, interventional Cardiology, Imelda Hospital, Bonheiden
AZ Sint-Jan Brugge-Oostende AV
Cardiology, Ruddershove 10, Belgium
UZ Leuven
Cardiology, Herestraat 49, 3000, Leuven
Jessa Ziekenhuis
Cardiology, Stadsomvaart 11, 3500, Hasselt
Copenhagen University Hospital
Cardiology, Blegdamsvej 9, 2100, Copenhagen Oe
Centre Hospitalier Regional Et Universitaire De Brest
Cardiology, Boulevard Tanguy Prigent, 29200, Brest
Centre Hospitalier Universitaire De Rennes
Cardiology, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Medico Chirurgical Ambroise Pare Hartmann
Cardiology, 25 Boulevard Victor Hugo, 92200, Neuilly-Sur-Seine
Societe D'Exploitation Du Centre Cardiologique Du Nord
Cardiology, 32 Rue Des Moulins Gemeaux, 93200, Saint-Denis
CHU Besancon
Cardiology, 3 Boulevard Alexandre Fleming, 25000, Besancon
Centre Hospitalier Universitaire De Bordeaux
Cardiology, Place Amelie Raba Leon, 33000, Bordeaux
Hopital Prive Jacques Cartier
Cardiology, 6 Avenue Du Noyer Lambert, 91300, Massy
Hôpital de la Pitié Salpêtrière
Cardiology, 47-83 Bd de l'Hôpital, 75013, Paris
University Hospital Of Clermont-Ferrand
Cardiology, 58 Rue Montalembert, 63000, Clermont-Ferrand
Centre Hospitalier Universitaire De Nantes
Cardiology, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain
Clinique Pasteur
Cardiology, 45 Avenue De Lombez, Cs 27617, Toulouse Cedex 3
Les Hopitaux Universitaires De Strasbourg
Cardiology, 1 Place De L Hopital, Cs 80426, Strasbourg Cedex
Centre Hospitalier Universitaire De Lille
Cardiology, Boulevard Du Professeur Jules Leclercq, 59000, Lille
APHP Bichat
Cardiology, 46 Rue Henri Huchard, France, Paris
Amphia Ziekenhuis te Breda
Cardiology, Molengracht 21, 4818 CK, Breda
Stichting OLVG
Cardiology, Oosterpark 9, 1091 AC, Amsterdam
Medisch Centrum Leeuwarden B.V.
Cardiology, Henri Dunantweg 2, 8934 AD, Leeuwarden
Radboud universitair medisch centrum Stichting
Cardiology, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Leiden University Medical Center
Cardiology, Albinusdreef 2, 2333 ZA, Leiden
Universitair Medisch Centrum Groningen
Cardiology, Hanzeplein 1, 9713 GZ, Groningen
Academic Medical Center at the University of Amsterdam
Cardiology, Meibergdreef 9, 1105 AZ, Amsterdam
St. Antonius Ziekenhuis
Cardiology, Koekoekslaan 1, 3435 CM, Nieuwegein
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2025-12-01 | 2025-12-01 | |||
| Denmark | 2026-01-05 | 2026-01-05 | |||
| France | 2024-10-15 | 2024-10-15 | |||
| Netherlands | 2023-12-21 | 2023-12-28 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 32 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1 Protocol 2023-504637-42-01 | 1.3 |
| Protocol (for publication) | D1 Protocol 2023-504637-42-01 TC | 1.3 |
| Recruitment arrangements (for publication) | K1 Recruitment arrangements POPular ATLANTIS FR V1 | 1 |
| Recruitment arrangements (for publication) | K1 Recruitment procedure POPular ATLANTIS | 2 |
| Recruitment arrangements (for publication) | K1 Recruitment procedure POPular ATLANTIS | 3 |
| Recruitment arrangements (for publication) | K1 Recruitment procedure POPular ATLANTIS | 2 |
| Recruitment arrangements (for publication) | K1 Recruitment procedure POPular ATLANTIS | 1 |
| Recruitment arrangements (for publication) | M3_Liste des centres en France | 2.1 |
| Subject information and informed consent form (for publication) | Dine rettigheder som forsgsperson i forsg med medicin _ De Videnskabsetiske Komiteer | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS BE | 2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS BE TC | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS DE | 2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS DK | 2.1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS FR | 2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF POPular ATLANTIS TC | 2 |
| Subject information and informed consent form (for publication) | Tillg til samtykkeblanket - Retten til ikke-viden | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 Acenocoumarol SmPC 1mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 Apixaban SmPC 2.5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 Apixaban SmPC 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 Clopidogrel SmPC 75mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Acetylsalicylzuur 80mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Coumadine 2mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Fenprocoumon 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Kardegic 75mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Mini-Sintrom 1mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Prasugrel 10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Ticagrelor 90mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Warfarin 2-5mg | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol synopsis ENG 2023-504637-42-01 | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol synopsis FR 2023-504637-42-01 | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol synopsis NL 2023-504637-42-01 | 1 |
Application history
11 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-07 | Netherlands | Acceptable 2023-11-13
|
2023-11-16 |
| 2 | SUBSEQUENT ADDITION OF MSC | APP-2 | 2024-02-13 | 2024-05-03 | ||
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-05-31 | |||
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-07-18 | Netherlands | Acceptable | 2024-08-16 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-11-09 | Netherlands | Acceptable 2025-01-14
|
2025-01-24 |
| 6 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-02-17 | Acceptable | 2025-04-08 | |
| 7 | SUBSEQUENT ADDITION OF MSC | APP-7 | 2025-04-28 | 2025-07-09 | ||
| 8 | SUBSEQUENT ADDITION OF MSC | APP-8 | 2025-04-28 | 2025-07-25 | ||
| 9 | SUBSEQUENT ADDITION OF MSC | APP-9 | 2025-04-28 | Acceptable 2023-11-13
|
2025-07-23 | |
| 10 | SUBSTANTIAL MODIFICATION | SM-8 | 2025-05-28 | Netherlands | Acceptable | 2025-06-18 |
| 11 | SUBSTANTIAL MODIFICATION | SM-9 | 2025-07-09 | Acceptable | 2025-08-25 |