Clinical trial NCT06215378: Antagonization of Heparin with Protamine Sulfate After TAVI
Official title: Antagonization of Heparin with Protamine Sulfate to Lower All Neurological Ischemic and Hemorrhagic Events After Transcatheter Aortic Valve Implantation for Aortic Stenosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Aortic Valve Stenosis
Heart Valve Diseases
Keywords: TAVI
Protamine
Heparine
Antagonization
Aortic stenosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Action Research Group
First posted: 2024-01-22
Enrollment: 940
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, national, multicenter, controlled, randomized open label study in 2 parallel groups at a 1:1 ratio
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Composite of ischemic and bleeding events
timeFrame: From procedure to hospital discharge (or at 30 days whichever comes first)
Secondary outcomes:
measure: In hospital stay
timeFrame: From procedure to hospital discharge, assessed up to 30 days
measure: Bleeding complication
timeFrame: From procedure to hospital discharge (or at 30 days whichever comes first)
measure: Assessement of interaction
timeFrame: From procedure to hospital discharge (or at 30 days whichever comes first)
measure: Assessement of adverse outcome
timeFrame: From procedure to hospital discharge (or at 30 days whichever comes first)
measure: Assessement of long term adverse outcome
timeFrame: From procedure 12 months post procedure
Other outcomes:
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