Antagonization of Heparin With Protamine Sulfate After TAVI (ATLANTIS-Prota)

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 3

Conditions: Heart Valve Diseases; Aortic Valve Stenosis

Treatments: Drug: Antagonization of heparin with protamine sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT06215378

APHP211046

Details and patient eligibility

About

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

Enrollment: 940 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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940 participants in 2 patient groups

Systematic heparine antagonization with protamine sulphate

Experimental group

Description:

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.

Treatment:

Drug: Antagonization of heparin with protamine sulfate

No Systematic heparine antagonization with protamine sulphate

No Intervention group

Description:

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