Antagonization of Heparin With Protamine Sulfate After TAVI

NCT06215378 | Recruiting Phase 3 DMC

• 1 other identifier: APHP211046
• Study Type: interventional
• Target: 940
• Locations: 1 country
• Sites: 1

Brief Summary

Transcatheter aortic valve replacement (TAVR) is now the first therapeutic option offered to high and intermediate risk patients with symptomatic aortic stenosis but even to low-risk, when the aortic valve is tricuspid and the transfemoral approach is suitable. Vascular and bleeding complications are the most frequent procedure-related unwanted events associated with increased short-term morbidity and mortality. Selection of the appropriate vascular access site and pre-closing devices as well as stent implantation mitigate these complications. ACT-guided heparin reaching a target of 300 seconds or more is recommended prior to the placement of the guiding sheath in the common femoral artery. Protamine sulfate is the heparin antidote, which antagonizes 100% of its anti-IIa activity and 60% of its anti-Xa activity. Reversal of heparin using protamine sulfate is recommended for transapical and complicated transfemoral aortic valve placement.However, there is a great heterogeneity of protamine use in daily practice and supportive evidence for the prevention of bleeding complications as well as its safety is lacking. In addition, the radial approach for the second vascular access is more commonly used as well as the use of echo-guided femoral puncture further questioning reversal of heparin when the procedure has been successfully completed without overt bleeding complications. Our study aims to demonstrate the superiority of a strategy of systematic ACT-guided heparin administration followed by systematic antagonization with protamine sulfate over usual of care to reduce in-hospital mortality, vascular/bleeding complications, stroke and transcient ischemic attack, myocardial infarction or red blood cell transfusion, from randomization to hospital discharge

Conditions

Aortic Valve Stenosis; Heart Valve Diseases

Keywords

TAVI; Protamine; Heparine; Antagonization; Aortic stenosis

Outcome Measures

Primary Outcomes (1)

• Composite of ischemic and bleeding events

  The primary endpoint is defined as the first occurrence, of any event of the composite of all-cause mortality, type 2, 3 or 4 bleeding, major or minor vascular complications, stroke or TIA, myocardial infarction or any redblood transfusion. The primary endpoint will be blindly determined by a clinical event committee according to the valve Academic Research Consortium-3 (VARC-3 classifications)

  From procedure to hospital discharge (or at 30 days whichever comes first)

Secondary Outcomes (5)

• In hospital stay

  From procedure to hospital discharge, assessed up to 30 days

• Bleeding complication

  From procedure to hospital discharge (or at 30 days whichever comes first)

• Assessement of interaction

  From procedure to hospital discharge (or at 30 days whichever comes first)

• Assessement of adverse outcome

  From procedure to hospital discharge (or at 30 days whichever comes first)

• Assessement of long term adverse outcome

  From procedure 12 months post procedure

Study Arms (2)

Systematic heparine antagonization with protamine sulphate

EXPERIMENTAL

Complete reversal of the Heparin administered during the TAVI achieved through the infusion of a protamine solution until the ACT returns to its baseline level.

Drug: Antagonization of heparin with protamine sulfate

No Systematic heparine antagonization with protamine sulphate

NO INTERVENTION

No administration of protamine solution unless a participant encounters a bleeding event requiring a surgery or percutanous intervention.

Interventions

Antagonization of heparin with protamine sulfate DRUG

A systematic use at the end of procedure of Protamine Sulfate for antagonization of heparine.1 mg of protamine sulfate neutralizes approximately 100 heparin unit. To be administered in slow infusion (10 min) not exceeding 50mg of protamine sulfate to reverse 100% of the anti-IIa activity of heparin sodium. If the ACT is not back to the baseline value after the end of this infusion, additional doses of protamine should be performed depending on the ACT value to obtain complete antagonization of anti-IIa activity of heparin sodium

Systematic heparine antagonization with protamine sulphate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥18 years of age
• Any patient eligible for transfemoral TAVI, irrespective of the chronic antithrombotic treatment
• Written informed consent
• Registered at the French social healthcare

You may not qualify if:

• Any major protamine sulfate exposure contraindications defined as a history of severe pulmonary hypertension, acute pulmonary edema or history of bronchospasm related to protamine sulfate administration
• Known allergy to protamine sulfate
• Hypersensitivity to protamine sulfate including protamine contained as an excipient in NPH \[Neutral Protamine Hagedorn\] insulin, known protamine or protamine-heparine complex antibodies
• Non-femoral approach for the TAVI procedure
• Protamine sulfate exposure within 24h of randomization
• Fish allergy
• Mechanical valves
• For men: Sterile or Vasectomy
• Women of childbearing potential
• Pregnancy and breast feeding women
• Contemporaneous enrolment in an interventional clinical trial
• Patient under guardianship or curatorship

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Action Research Group: collaborator

Study Sites (1)

Pitié Salpêtrière hospital

Paris, Île-de-France Region, 75013, France

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis; Heart Valve Diseases

Interventions

Protamines

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Nuclear Proteins; Proteins; Amino Acids, Peptides, and Proteins; Nucleoproteins

Central Study Contacts

Paul Dr GUEDENEY, MD

CONTACT

0184827619; paul.guedeney@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The members of the endpoint committee will evaluate events related to both primary and secondary outcomes in a blinded manner, ensuring they are unaware of patient identities and the groups to which they were allocated through randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, national, multicenter, controlled, randomized open label study in 2 parallel groups at a 1:1 ratio

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 22, 2024
• Study Start: May 25, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 22, 2025

Record last verified: 2025-01

Locations

FR (1)