Antagonization of Heparin With Protamine Sulfate After TAVI

NCT ID: NCT06215378

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 940 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-25
• Study Completion Date: 2027-03-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Systematic heparine antagonization with protamine sulphate

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.

Group Type: EXPERIMENTAL

Antagonization of heparin with protamine sulfate

Intervention Type: 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

No Systematic heparine antagonization with protamine sulphate

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Antagonization of heparin with protamine sulfate

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Action Research Group

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pitié Salpêtrière hospital

Paris, Île-de-France Region, France

Site Status: RECRUITING

Countries

France

Central Contacts

Paul Dr GUEDENEY, MD

Role: CONTACT

paul.guedeney@aphp.fr

0184827619 ext. +33

Facility Contacts

Paul GUEDENEY, MD, PHD

Role: primary

Other Identifiers

APHP211046

Identifier Type: -

Identifier Source: org_study_id