NCT05774691

Brief 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. 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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,000

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2023

Typical duration for phase_4

Geographic Reach
2 countries

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 3, 2023

Completed
17 days until next milestone

First Posted

Study publicly available on registry

March 20, 2023

Completed
8 months until next milestone

Study Start

First participant enrolled

November 1, 2023

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

November 26, 2025

Status Verified

November 1, 2025

Enrollment Period

2.1 years

First QC Date

March 3, 2023

Last Update Submit

November 20, 2025

Conditions

Aortic Valve Stenosis

Keywords

TAVITAVRBleedingMortalityAllergyProtamine

Outcome Measures

Primary Outcomes (1)

  • Composite of all-cause mortality or type 1-4 bleeding

    According to the VARC-3 criteria

    30 days after TAVI

Secondary Outcomes (5)

  • All bleeding

    30 days after TAVI

  • Major, life-threatening or fatal bleeding

    30 days after TAVI

  • Major vascular complications

    30 days after TAVI

  • Cardiovascular mortality

    30 days after TAVI

  • All-cause mortality

    30 days after TAVI

Other Outcomes (34)

  • Safety endpoint: Anaphylaxis

    30 days after TAVI

  • Safety endpoint: Thromboembolic events

    30 days after TAVI

  • Neurologic events

    30 days after TAVI

  • +31 more other outcomes

Study Arms (2)

Routine protamine administration

ACTIVE COMPARATOR

Routine protamine administration in a ratio of 1 IE per 1 IE of unfractionated heparin.

Drug: Protamine sulfate

Selective protamine administration

ACTIVE COMPARATOR

Selective protamine administration, in case of (threatening) bleeding.

Drug: Protamine sulfate

Interventions

Protamine sulfateDRUG

Routine protamine administration in a ratio of 1 IE per 1 IE of unfractionated heparin.

Also known as: Routine heparin reversal
Routine protamine administration

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged \> 18 years
  • Undergoing transfemoral TAVI with any commercially available transcatheter heart valve
  • Provided written informed consent

You may not qualify if:

  • Documented protamine allergy or anaphylaxis
  • Recent PCI (\< 3 months before TAVI)
  • Planned arterial access via surgical cut-down

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

A.S.Z. Aalst

Aalst, Belgium

RECRUITING

University Hospitals Leuven

Leuven, Belgium

RECRUITING

Maastricht UMC

Maastricht, Limburg, Netherlands

NOT YET RECRUITING

Leiden University Medical Center

Leiden, South Holland, Netherlands

RECRUITING

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands

RECRUITING

Amsterdam University Medical Center

Amsterdam, Netherlands

NOT YET RECRUITING

Related Publications (1)

  • 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.

    PMID: 41177203DERIVED

MeSH Terms

Conditions

Aortic Valve StenosisHemorrhageHypersensitivity

Interventions

Protamines

Condition Hierarchy (Ancestors)

Aortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow ObstructionPathologic ProcessesPathological Conditions, Signs and SymptomsImmune System Diseases

Intervention Hierarchy (Ancestors)

Nuclear ProteinsProteinsAmino Acids, Peptides, and ProteinsNucleoproteins

Central Study Contacts

Prof. J.M. ten Berg, MD, PhD

CONTACT

0031 088 320 3000jurtenberg@gmail.com

D.C. Overduin, MD

CONTACT

0031 088 320 3000c.overduin@antoniusziekenhuis.nl

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Parallel Assignment
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

March 3, 2023

First Posted

March 20, 2023

Study Start

November 1, 2023

Primary Completion

December 1, 2025

Study Completion

December 1, 2025

Last Updated

November 26, 2025

Record last verified: 2025-11

Locations

BE(2)NL(4)