Optimal PeriproCeduraL AnticOagulation in Structural Transseptal Interventions

Study Overview
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Brief Summary
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The transcatheter edge to edge mitral valve repair (TEER) and left atrial appendage closure (LAAC) are the interventional cardiology procedures that require periprocedural anticoagulation with unfractionated heparin (UFH). The UFH is administered either before or immediately after transseptal puncture, at the discretion of the operator The aim of the study is to establish the optimal timing of initiation of periprocedural anticoagulation in patients undergoing structural heart interventions requiring transseptal puncture (TEER and LAAC), Patients who undergo TEER implantation or LAAC procedure will be randomized to two groups: Early UFH administration. The iv. bolus of UFH (100Units/kg) will be given after obtained femoral vein access and at least 5 minutes prior to the start of the TSP. Late UFH administration. The iv. bolus of UFH (100Units/kg) will be given immediately after TSP, defined as the introduction of transseptal sheath into the left atrium.

Official Title
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Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions

Conditions
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Mitral Regurgitation, Atrial Fibrillation, Anticoagulation

Intervention / Treatment
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* Other: early anticoagulation
* Other: late anticoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 years Planned TEER procedure or left atrial appendage closure The patient is willing to sign informed consent and comply will all study procedure Exclusion Criteria: Women who are pregnant or breastfeeding and those women of childbearing potential who do not agree to use at least two contraceptive measures (oral contraception, mechanical contraception, approved contraceptive implants, intrauterine device, tubal ligation). The criterion does not apply to women who have been postmenopausal for at least 2 years prior to study enrollment (defined as at least one year without menstrual periods) or underwent surgical sterilization procedure. All eligible women who are younger than 55 years must have negative pregnancy test within 24 hours prior to randomization. Congenital or acquire bleeding disorders (i.e.diagnosed thrombophilia, bleeding diathesis, thrombocyopenia with platelet count <50 thousand/ml, INR elevated >1.5 in the last test prior to randomization) INR > 1.5 within 24 hours prior to the procedure in patients chronically treated with vitamin K antagonists. (applies to the last INR value prior to randomization) Last dose of new oral anticoagulant < 48 hours prior to the procedure (assessed at randomization) Last dose of low molecular weight heparin <12 hours prior to the procedure (assessed at randomization) Contraindications to MR imaging (i.e. claustrophobia, ferromagnetic intraocular foreign boddies, ferromagnetic metalic prostheses) Implanted cardiac devices for electrotherapy if: device has epicardial leads left disconnected leads or non-functional or damaged devices device implanted within abdominal wall the patient is pacemaker dependant (lack of escape rhytm >30/min) the device was implanted or exchanged within 6 weeks prior to the MR examination device mulfunction identified during the control performed prior to the MR examination, that in the opinion of electrophysiologist team may impact the safety of MR imaging low voltage of the device battery - the battery on the examination day should have at least 20% of the voltage value between the nominal value and elective replacement indicator (ERI) value, or the expected battery life calculated by the device should equal or exceed one year.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to: Early unfractionated heparin administration. The iv. bolus of UFH (100Units/kg) will be given after obtained femoral vein access and at least 5 minutes prior to the start of the TSP. Late unfractionated heparin administration. The iv. bolus of UFH (100Units/kg) will be given immediately after TSP, defined as the introduction of transseptal sheath into the left atrium.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early UFH administration<br>The iv. bolus of UFH (100Units/kg) will be given after obtained femoral vein access and at least 5 minutes prior to the start of the TSP. | Other: early anticoagulation<br>* Anticoagulation prior to transseptal puncture<br>|
| Active Comparator: Late UFH administration<br>The iv. bolus of UFH (100Units/kg) will be given immediately after TSP, defined as the introduction of transseptal sheath into the left atrium. | Other: late anticoagulation<br>* Anticoagulation after transseptal puncture<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. MACCE 2. Intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transsesophageal echocardiography 3. Occurrence of new ischemic lesions with diameter ≥4 mm in brain MR performed 2-5 days after procedure | Major adverse cardiac and cerebrovascular events (MACCE) will include: death, stroke, TIA, peripheral embolization, myocardial infarction within 30 days from the index procedure. | Within 30 days from the index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate and severe bleeding complications (BARC 2-5) including cardiac tamponade requiring intervention during the index hospitalization |  | during the hospitalization related to the index procedure but up to 30 days from randomization | 
| Intraprocedural fresh thrombus formation in the right of left atrium as assessed with periprocedural transsesophageal echocardiography |  | during index procedure | 
| Occurrence of new ischemic brain lesion in the MR examination performed within 2-5 days post index procedure. |  | within 2-5 days post index procedure | 
| Major adverse cardiac and cerebrovascular events (death, stroke, TIA, peripheral embolization, myocardial infarction) within 30 days from the index procedure. |  | within 30 days from index procedure |