Protamine Sulfate During Transcatheter Aortic Valve Implantation

Study Overview
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Brief Summary
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Transcatheter aortic valve implantation (TAVI) is a new, rapidly emerging standard of care in inoperable and high-risk patients with severe, symptomatic aortic stenosis. Information regarding reversal of unfractionated heparin with protamine sulfate in order to facilitate access site closure is scarce and based on expert consensus. Clinical practice varies between centers. Protamine sulphate may decrease the amount of bleeding complications related to the access-site. The impact on possible thromboembolic complications is unknown. Both bleeding and thromboembolic complications increase mortality after TAVI. A randomized trial is required in order to assess impact of protamine sulfate on prevalence and extent of bleeding and thromboembolic complications.

Detailed Description
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Information regarding reversal of unfractionated heparin (UFH) with protamine sulfate (PS) is based on expert consensus from 2012, which recommends use of UFH in order to achieve activated clotting time (ACT) > 300 seconds as well as UFH reversal with PS in case of TAVI via transapical access as well as transfemoral access with the exception of cases with minimal bleeding risk. However, the clinical practice varies between centers - some use PS routinely, others - only in selected cases. The actual impact of PS on bleeding complications reduction is unknown. Furthermore, a pro-thromboembolic effect of the PS cannot be excluded. Both bleeding (major and life-threatening according to Valve Academic Research Consortium [VARC] criteria) and thromboembolic complications increase mortality after TAVI. The occurrence of these complications in international TAVI registries in 30-day observation ranges from 9.7% in case of major bleeding, 4.7% in case of life-threatening bleeds and 5% in case of strokes. There are no randomized studies assessing impact of PS on frequency of bleeding and thromboembolic complications after TAVI, its side-effects and influence on mortality. Randomized trial is required in order to assess impact of protamine sulfate on prevalence of bleeding and thromboembolic complications.

Official Title
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Use of Protamine Sulfate During Transcatheter Aortic Valve Implantation - Impact on Bleeding and Thromboembolic Complications

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Drug: Protamine sulfate
* Drug: 0.9% NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who underwent successful TAVI with any approved TAVI device via transfemoral access with use of any of the approved vascular closure devices provided written informed consent Exclusion Criteria: no consent periprocedural complications requiring continuation of heparin or administration of protamine sulfate alergy to fish, protamine, protamine derivates, history of Humulin N, Novolin N, Novolin NPH, Gensulin N, SciLin N, NPH Iletin II and isophane insulin intake

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Protamine sulfate<br>After obtaining optimal valve deployment patients will receive protamine sulfate (1 mg for each 100 units of UFH i.v.). Measurement of activated clotting time (ACT) will be performed (after heparin administration and after protamine sulfate administration). | Drug: Protamine sulfate<br> <br> |
| Placebo Comparator: 0.9% NaCl<br>After obtaining optimal valve deployment patients will receive 0.9% saline (20 ml i.v.). Measurement of activated clotting time (ACT) will be performed (after heparin administration and after placebo administration). | Drug: 0.9% NaCl<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding complications | Composite of life-threatening and major bleeding complications according to Valve Academic Research Consortium (VARC) criteria (unit of measure: 0/1 [absence/presence]) | 48 hours or hospital discharge, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful closure of the access-site | Angiographic assessment of contrast extravasation from the access site after closure with preclose device at the end of the procedure. Unit of measure: 0/1 (absence/presence). | 15 minutes | 
| Thromboembolic complications | Clinical assessment of thromboembolic complications in the central nervous system and peripheral vasculature (e.g. mesenteric, extremities). Unit of measure: 0/1 (absence/presence) | 5 days or hospital discharge, whichever occurs first | 
| Assessment of peri-procedural myocardial muscle injury | Measurements of levels of high sensitivity cardiac troponin T and isoenzyme MB of creatine kinase before the procedure and 6- and 12-24 hours after the procedure. Unit of measure: high sensitivity cardiac troponin T [ng/L], isoenzyme MB of creatine kinase [mcg/L]. | 24 hours | 
| All-cause mortality | All-cause mortality. Unit of measure: 0/1 (absence/presence). | 30 days |