Antagonization of Heparin With Protamine Sulfate After TAVI

Phase 3

Not yet recruiting

• Conditions: Aortic Valve Stenosis; Heart Valve Diseases
• Interventions: Drug: Antagonization of heparin with protamine sulfate

• Registration Number: NCT06215378
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-12
• Study First Submitted: 2023-12-22
• Study First Submitted QC: 2024-01-10
• Study First Posted: 2024-01-22
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Study Start: 2024-10-01
• Primary Completion: 2026-10-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 940

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Systematic heparine antagonization with protamine sulphate	Antagonization of heparin with protamine sulfate	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.

Primary Outcome Measures

Name	Time	Method
Composite of ischemic and bleeding events	From procedure to hospital discharge (or at 30 days whichever comes first)	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)

Secondary Outcome Measures

Name	Time	Method
In hospital stay	From procedure to hospital discharge, assessed up to 30 days	Assessment of length of in-hospital stay in days post TAVI procedure
Assessement of adverse outcome	From procedure to hospital discharge (or at 30 days whichever comes first)	Assessment of the occurrence of: * Death or type 2, 3 or 4 bleedings; * Any kidney injury, stage 2 to 4 according to the KDIGO definition; * Death, type 2, 3 or 4 bleedings or stroke; * Death, VARC 3 type 2-3-4 bleeding or Any red blood cell transfusion, MI or stroke Or TIA; * Any myocardial infarction, stroke or TIA; * Type 3 or 4 bleeding; * Type 2 bleeding; * Minor vascular complications; * Access site and access related vascular injury according to VARC-3 criteria
Bleeding complication	From procedure to hospital discharge (or at 30 days whichever comes first)	Assessment of the occurrence of: * Type 2, 3 or 4 bleeding according to the VARC 3 criteria or any red blood cell transfusion of minor or vascular complications.; * Type 2, 3 or 4 bleedings or red blood cell transfusion.; * Any red blood cell transfusion; * Type 2, 3 or 4 bleedings
Assessement of long term adverse outcome	From procedure 12 months post procedure	Assessment of the composite of: Death, stroke, TIA, MI and bleeding VARC type 2 or more as well as each individual endpoint
Assessement of interaction	From procedure to hospital discharge (or at 30 days whichever comes first)	Assessment of an interaction in the impact of systematic antagonization according to the use or not of an echo-guided femoral puncture and/or arterial radial access. These subgroups are defined at the time of randomization by stratification.