ClinicalTrials.gov
ClinicalTrials.gov Menu

Protamine Sulfate During Transcatheter Aortic Valve Implantation (PS TAVI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02974660
Recruitment Status : Recruiting
First Posted : November 28, 2016
Last Update Posted : March 13, 2018
Sponsor:
Information provided by (Responsible Party):
Medical University of Warsaw

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 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 : December 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : January 2019


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



Primary Outcome Measures :
  1. Bleeding complications [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 30 days ]
    All-cause mortality. Unit of measure: 0/1 (absence/presence).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974660


Contacts
Contact: Karol Zbroński, MD 0048607516810 karol.zbronski@gmail.com
Contact: Zenon Huczek, MD PhD 0048692433568 zhuczek@wp.pl

Locations
Poland
First Department of Cardiology, Medical University of Warsaw Recruiting
Warsaw, Poland
Contact: Karol Zbronski, MD    0048607516810    karol.zbronski@gmail.com   
Contact: Zenon Huczek, MD PhD       zhuczek@wp.pl   
Sponsors and Collaborators
Medical University of Warsaw

Publications of Results:
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 RA, Bhatt DL, Ferrari VA, Fisher JD, Garcia MJ, Gardner TJ, Gentile F, Gilson MF, Hernandez AF, Jacobs AK, Kaul S, Linderbaum JA, Moliterno DJ, Weitz HH; American Heart Association; American Society of Echocardiography; European Association for Cardio-Thoracic Surgery; Heart Failure Society of America; Mended Hearts; Society of Cardiovascular Anesthesiologists; Society of Cardiovascular Computed Tomography; Society for Cardiovascular Magnetic Resonance. 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement: developed in collabration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Thorac Cardiovasc Surg. 2012 Sep;144(3):e29-84. doi: 10.1016/j.jtcvs.2012.03.001.

Other Publications:
Responsible Party: Medical University of Warsaw
ClinicalTrials.gov Identifier: NCT02974660     History of Changes
Other Study ID Numbers: WUM-KZ
First Posted: November 28, 2016    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Protamines
Heparin Antagonists
Molecular Mechanisms of Pharmacological Action
Coagulants