A Phase 3 interventional study of Antagonization of heparin with protamine sulfate in Aortic Valve Stenosis and Heart Valve Diseases, sponsored by Assistance Publique - Hôpitaux de Paris. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-22.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment
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
985 studies on the registry are indexed under Aortic Valve Stenosis; 283 are open to participants now.
This study's planned enrollment of 940 is above the median of 120 across 525 interventional studies indexed under Aortic Valve Stenosis.
Browse Aortic Valve Stenosis studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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 administration of protamine solution unless a participant encounters a bleeding event requiring a surgery or percutanous intervention.
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
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)
Time frame: From procedure to hospital discharge (or at 30 days whichever comes first)
In hospital stay
Assessment of length of in-hospital stay in days post TAVI procedure
Time frame: From procedure to hospital discharge, assessed up to 30 days
Bleeding complication
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
Time frame: From procedure to hospital discharge (or at 30 days whichever comes first)
Assessement of interaction
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.
Time frame: From procedure to hospital discharge (or at 30 days whichever comes first)
Assessement of adverse outcome
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
Time frame: From procedure to hospital discharge (or at 30 days whichever comes first)
Assessement of long term adverse outcome
Assessment of the composite of: Death, stroke, TIA, MI and bleeding VARC type 2 or more as well as each individual endpoint
Time frame: From procedure 12 months post procedure
Plan to share: Undecided
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