PS TAVI: Protamine Sulfate During Transcatheter Aortic Valve Implantation

• Sponsor: Medical University of Warsaw (Other)
• Overall Status: Completed
• CT.gov ID: NCT02974660
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis	Drug: Protamine sulfate; Drug: 0.9% NaCl	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Use of Protamine Sulfate During Transcatheter Aortic Valve Implantation - Impact on Bleeding and Thromboembolic Complications
• Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Jul 1, 2020
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Protamine sulfate 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
Placebo Comparator: 0.9% NaCl 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

Outcome Measures

Primary Outcome Measures

1. Bleeding complications [48 hours or hospital discharge, whichever occurs first]

   Composite of life-threatening and major bleeding complications according to Valve Academic Research Consortium (VARC) criteria (unit of measure: 0/1 [absence/presence])

Secondary Outcome Measures

1. Successful closure of the access-site [15 minutes]

   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).

2. Thromboembolic complications [5 days or hospital discharge, whichever occurs first]

   Clinical assessment of thromboembolic complications in the central nervous system and peripheral vasculature (e.g. mesenteric, extremities). Unit of measure: 0/1 (absence/presence)

3. Assessment of peri-procedural myocardial muscle injury [24 hours]

   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].

4. All-cause mortality [30 days]

   All-cause mortality. Unit of measure: 0/1 (absence/presence).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	First Department of Cardiology, Medical University of Warsaw	Warsaw		Poland

Sponsors and Collaborators

• Medical University of Warsaw

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Medical University of Warsaw
• ClinicalTrials.gov Identifier: NCT02974660
• Other Study ID Numbers: WUM-KZ
• First Posted: Nov 28, 2016
• Last Update Posted: Oct 22, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Aortic Valve Stenosis; Protamines

Study Results

No Results Posted as of Oct 22, 2020