Aortic Valve StenosisPhase 4NCT05774691
Routine Versus Selective Protamine Administration to Reduce Bleeding Complications After Transcatheter Aortic Valve Implantation (POPular ACE TAVI)
A Phase 4 study testing Protamine sulfate in people with Aortic Valve Stenosis, run by St. Antonius Hospital at 6 sites in 2 countries.
Trial summary
Heparin reversal by protamine administration after transcatheter aortic valve implantation (TAVI) may reduce bleeding events. However, protamine can also cause life-threatening allergic reactions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Stenosis
- What is being tested?
- Protamine sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 1 Nov 2023to 2 Jan 2026
- 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
- Aged > 18 years
- Undergoing transfemoral TAVI with any commercially available transcatheter heart valve
- Provided written informed consent
Who cannot join
- Documented protamine allergy or anaphylaxis
- Recent PCI (< 3 months before TAVI)
- Planned arterial access via surgical cut-down
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Netherlands4 sites
Amsterdam University Medical Center
Amsterdam
Leiden University Medical Center
Leiden, South Holland
Maastricht UMC
Maastricht, Limburg
St. Antonius Hospital
Nieuwegein, Utrecht
About this study
Official title: Routine Versus Selective Protamine Administration to Reduce Bleeding Complications After Transcatheter Aortic Valve Implantation
Heparin reversal by protamine administration after transcatheter aortic valve implantation (TAVI) may reduce bleeding events. However, protamine can also cause life-threatening allergic reactions. High-quality evidence regarding the clinical safety and efficacy of routine protamine administration after TAVI is lacking.
The aim of this clinical trial is to determine if routine protamine administration, compared with selective protamine administration, reduces the risk of all-cause mortality or clinically relevant bleeding within 30 days after transcatheter aortic valve implantation.
- Conditions
- Aortic Valve Stenosis
- Being tested
- Protamine sulfate
- Keywords
- TAVI, TAVR, Bleeding, Mortality, Allergy, Protamine
- Medical subject headings
- Aortic Valve Stenosis, Hemorrhage, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protamine sulfateDrug
Also called Routine heparin reversal
Routine protamine administration in a ratio of 1 IE per 1 IE of unfractionated heparin.
Protamine sulfateDrug
Also called Selective heparin reversal
Selective protamine administration, in case of (threatening) bleeding
| Study group | Role | What they receive |
|---|---|---|
| Routine protamine administration | Active comparator | Routine protamine administration in a ratio of 1 IE per 1 IE of unfractionated heparin. Receives: Drug: Protamine sulfate |
| Selective protamine administration | Active comparator | Selective protamine administration, in case of (threatening) bleeding. Receives: Drug: Protamine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of all-cause mortality or type 1-4 bleeding
According to the VARC-3 criteria
Measured: 30 days after TAVI
Secondary outcomes (5)
All bleeding
According to the VARC-3 criteria type 1-4 bleeding
Measured: 30 days after TAVI
Major, life-threatening or fatal bleeding
According to the VARC-3 criteria type 2-4 bleeding
Measured: 30 days after TAVI
Major vascular complications
According to the VARC-3 criteria
Measured: 30 days after TAVI
Cardiovascular mortality
According to the VARC-3 criteria
Measured: 30 days after TAVI
All-cause mortality
According to the VARC-3 criteria
Measured: 30 days after TAVI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start1 Nov 2023
- Primary completion2 Jan 2026
- Study completion2 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve StenosisStudies 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
- Model description
- Parallel Assignment
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Antonius Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- St. Antonius Research Fund
- Responsible party
- Principal investigator, Jurriën M. ten Berg, MD, PhD, St. Antonius Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05774691
- Sponsor's protocol ID
- 2023-504205-36-00
- Other IDs
- 2023
- Status last verified
- May 2026
- First submitted
- 3 Mar 2023
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Overduin DC, van Ginkel DJ, Dubois C, Lesizza P, Broeze GM, Montero-Cabezas JM, Rosseel L, van der Kley F, van Nuland PJ, Smits TP, Hemelrijk KI, Aarts HM, Rensing BJWM, Timmers L, Swaans MJ, Sonker U, Veenstra L, van 't Hof AWJ, Peper J, Tijssen JGP, Delewi R, Vriesendorp PA, Ten Berg JM. Routine versus selective protamine administration to reduce bleeding after TAVI: Rationale and design of the POPular ACE TAVI trial. Am Heart J. 2026 Mar;293:107296. doi: 10.1016/j.ahj.2025.107296. Epub 2025 Oct 31.
PubMed 41177203
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Routine Versus Selective Protamine Administration to Reduce Bleeding Complications After Transcatheter Aortic Valve Implantation
- ClinicalTrials.gov ID
- NCT05774691
- Acronym / sponsor ID
- 2023-504205-36-00
- Conditions
- Aortic Valve Stenosis
- Keywords
- TAVI, TAVR, Bleeding, Mortality, Allergy, Protamine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- St. Antonius HospitalUniversity, hospital or other
- Collaborators
- St. Antonius Research Fund
- Study start
- 1 Nov 2023 (actual)
- Primary completion
- 2 Jan 2026 (actual)
- Study completion
- 2 Jan 2026 (actual)
- First posted
- 20 Mar 2023 (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.
Heparin reversal by protamine administration after transcatheter aortic valve implantation (TAVI) may reduce bleeding events. However, protamine can also cause life-threatening allergic reactions. High-quality evidence regarding the clinical safety and efficacy of routine protamine administration after TAVI is lacking.
The aim of this clinical trial is to determine if routine protamine administration, compared with selective protamine administration, reduces the risk of all-cause mortality or clinically relevant bleeding within 30 days after transcatheter aortic valve implantation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Routine protamine administration | Active comparator | Drug: Protamine sulfateRoutine protamine administration in a ratio of 1 IE per 1 IE of unfractionated heparin. |
| Selective protamine administration | Active comparator | Drug: Protamine sulfateSelective protamine administration, in case of (threatening) bleeding. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Aged > 18 years
- Undergoing transfemoral TAVI with any commercially available transcatheter heart valve
- Provided written informed consent
Key exclusion criteria (3 listed)
- Documented protamine allergy or anaphylaxis
- Recent PCI (< 3 months before TAVI)
- Planned arterial access via surgical cut-down
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 |
|---|---|---|
| Protamine sulfateAlso: Routine heparin reversalRoutine protamine administration in a ratio of 1 IE per 1 IE of unfractionated heparin. | Drug | Routine protamine administration |
| Protamine sulfateAlso: Selective heparin reversalSelective protamine administration, in case of (threatening) bleeding | Drug | Selective protamine administration |
Primary outcome
Composite of all-cause mortality or type 1-4 bleeding
Time frame: 30 days after TAVI
According to the VARC-3 criteria
5 secondary outcomes
All bleeding
Time frame: 30 days after TAVI
Major, life-threatening or fatal bleeding
Time frame: 30 days after TAVI
Major vascular complications
Time frame: 30 days after TAVI
Cardiovascular mortality
Time frame: 30 days after TAVI
All-cause mortality
Time frame: 30 days after TAVI
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 20 May 2026.
- Derived from this study: PubMed 41177203Overduin DC, van Ginkel DJ, Dubois C, Lesizza P, Broeze GM, Montero-Cabezas JM, Rosseel L, van der Kley F, van Nuland PJ, Smits TP, Hemelrijk KI, Aarts HM, Rensing BJWM, Timmers L, Swaans MJ, Sonker U, Veenstra L, van 't Hof AWJ, Peper J, Tijssen JGP, Delewi R, Vriesendorp PA, Ten Berg JM. Routine versus selective protamine administration to reduce bleeding after TAVI: Rationale and design of the POPular ACE TAVI trial. Am Heart J. 2026 Mar;293:107296. doi: 10.1016/j.ahj.2025.107296. Epub 2025 Oct 31.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Protamine sulfate in people with Aortic Valve Stenosis, run by St. Antonius Hospital at 6 sites in 2 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 3 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 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands, Belgium. 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?
Composite of all-cause mortality or type 1-4 bleeding (time frame: 30 days after TAVI). 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 NCT05774691, which also lists 1 linked publication.
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 20 May 2026.