Overview
Sponsor-declared trial summary
Aortic stenosis
To determine if routine protamine administration, compared with selective protamine administration, reduces the risk of the composite endpoint of all-cause death or clinically relevant bleeding within 30 days after TAVI.
Key facts
- Sponsor
- St Antonius Hospital
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Trial duration
- 1 Nov 2023 → 2 Jan 2026
- Decision date (initial)
- 2023-10-10
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- St. Antonius Research Fund
External identifiers
- EU CT number
- 2023-504205-36-00
- WHO UTN
- U1111-1289-5421
- ClinicalTrials.gov
- NCT05774691
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To determine if routine protamine administration, compared with selective protamine administration, reduces the risk of the composite endpoint of all-cause death or clinically relevant bleeding within 30 days after TAVI.
Secondary objectives 5
- The risk of all bleeding (VARC-3 type 1-4)
- The risk of major bleeding, life-threatening or fatal bleeding (VARC-3 type 2-4)
- The risk of major vascular complications (VARC-3)
- The risk of cardiovascular mortality (VARC-3)
- The risk of all-cause mortality (VARC-3)
Conditions and MedDRA coding
Aortic stenosis
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Aged > 18 years
- Undergoing transfemoral TAVI with any commercially available transcatheter heart valve
- Provided written informed consent
Exclusion criteria 3
- Documented protamine allergy or anaphylaxis
- Recent PCI (< 3 months before TAVI)
- Planned arterial access via surgical cut-down
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The composite of cardiovascular mortality or clinically relevant bleeding (VARC-3 type 1-4) within 30 days after TAVI procedure.
Secondary endpoints 5
- All bleeding (VARC-3 type 1-4)
- Major, life-threatening or fatal bleeding (VARC-3 type 2-4)
- Major vascular complications (VARC-3)
- Cardiovascular mortality (VARC-3)
- All-cause mortality
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Protamine sulfaat LEO Pharma 1400 anti-heparine IE/ml oplossing voor injectie en infusie
PRD427827 · Product
- Active substance
- Protamine Sulfate
- Substance synonyms
- PROTAMINE SULPHATE
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- DIRECT INTRAVENOUS INJECTION
- Max daily dose
- 14000 IU international unit(s)
- Max total dose
- 14000 IU international unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V03AB14 — PROTAMINE
- Marketing authorisation
- BE316985
- MA holder
- LEO PHARMA A/S
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
NaCl 0,9 % B. Braun, oplossing voor infusie
PRD5372758 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS BOLUS INJECTION/IV INFUSION
- Max daily dose
- 10 ml millilitre(s)
- Max total dose
- 10 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05BB01 — ELECTROLYTES
- Marketing authorisation
- BE138476
- MA holder
- B.BRAUN MELSUNGEN AG
- MA country
- Belgium
- 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
- Dirk-Jan van Ginkel
Public contact point
- Organisation
- St Antonius Hospital
- Contact name
- Dirk-Jan van Ginkel
Locations
2 EU/EEA countries · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ended | 200 | 2 |
| Netherlands | Ended | 600 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
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 | 2024-03-01 | 2025-11-12 | 2024-03-01 | 2025-09-18 | |
| Netherlands | 2023-11-01 | 2026-01-02 | 2023-11-01 | 2025-09-18 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1 Protocol 2023-504205-36-00 | 2.1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC NaCl | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Protamine sulfaat | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol synopsis DE 2023-504205-36-00 | 2 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis ENG 2023-504205-36-00 | 3 |
| Synopsis of the protocol (for publication) | D1 Protocol synopsis FR 2023-504205-36-00 | 2 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis NL 2023-504205-36-00 | 3 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-23 | Netherlands | Acceptable 2023-06-13
|
2023-06-13 |
| 2 | SUBSEQUENT ADDITION OF MSC | APP-2 | 2023-08-01 | 2023-10-10 | ||
| 3 | SUBSTANTIAL MODIFICATION | SM-6 | 2023-11-23 | Netherlands | Acceptable 2024-01-23
|
2024-01-23 |
| 4 | SUBSTANTIAL MODIFICATION | SM-7 | 2024-04-02 | Netherlands | Acceptable | 2024-04-23 |
| 5 | SUBSTANTIAL MODIFICATION | SM-9 | 2025-08-29 | Netherlands | Acceptable 2025-11-19
|
2025-11-20 |