Protamine Sulfate During Transcatheter Aortic Valve Implantation

Aortic Valve Stenosis Clinical Trial

— PS TAVI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02974660
• Other study ID #: WUM-KZ
• Status: Completed
• Phase: Phase 4
• Start date: December 2016
• Est. completion date: September 2020

Study information

• Verified date: October 2020
• Source: Medical University of Warsaw
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Stenosis

Intervention

Drug:
• Protamine sulfate

• 0.9% NaCl

Locations

Country	Name	City	State
Poland	First Department of Cardiology, Medical University of Warsaw	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Warsaw

Country where clinical trial is conducted

Poland, 

References & Publications (6)

Borz B, Durand E, Godin M, Tron C, Canville A, Litzler PY, Bessou JP, Cribier A, Eltchaninoff H. Incidence, predictors and impact of bleeding after transcatheter aortic valve implantation using the balloon-expandable Edwards prosthesis. Heart. 2013 Jun;99 — View Citation

Gauthier C, Astarci P, Baele P, Matta A, Kahn D, Kefer J, Momeni M. Mid-term survival after transcatheter aortic valve implantation: Results with respect to the anesthetic management and to the access route (transfemoral versus transapical). Ann Card Anae — View Citation

Holmes DR Jr, Mack MJ, Kaul S, Agnihotri A, Alexander KP, Bailey SR, Calhoon JH, Carabello BA, Desai MY, Edwards FH, Francis GS, Gardner TJ, Kappetein AP, Linderbaum JA, Mukherjee C, Mukherjee D, Otto CM, Ruiz CE, Sacco RL, Smith D, Thomas JD, Harrington — View Citation

Kappetein AP, Head SJ, Généreux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodés-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Eur Heart J. 2012 Oct;33(19):2403-18. doi: 10.1093/eurheartj/ehs255. — View Citation

Linke A, Wenaweser P, Gerckens U, Tamburino C, Bosmans J, Bleiziffer S, Blackman D, Schäfer U, Müller R, Sievert H, Søndergaard L, Klugmann S, Hoffmann R, Tchétché D, Colombo A, Legrand VM, Bedogni F, lePrince P, Schuler G, Mazzitelli D, Eftychiou C, Frer — View Citation

Rodés-Cabau J, Dauerman HL, Cohen MG, Mehran R, Small EM, Smyth SS, Costa MA, Mega JL, O'Donoghue ML, Ohman EM, Becker RC. Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events. J Am Coll Car — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	All-cause mortality	All-cause mortality. Unit of measure: 0/1 (absence/presence).	30 days