Antagonization of Heparin With Protamine Sulfate After TAVI
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris
About this trial
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
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Antagonization of heparin with protamine sulfate
DrugA 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
Treatment groups
940 Participants
are divided into 2 treatment groupsGroup A: Systematic heparine antagonization with protamine sulphateExperimental treatment 1 intervention
Group B: No Systematic heparine antagonization with protamine sulphateNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
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)Secondary outcomes
1
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 days2
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)3
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)4
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)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Assistance Publique - Hôpitaux de Paris
Lead sponsor
Action Research Group
Collaborator
Source ClinicalTrials.gov