Transcranial Doppler (TCD) Assessment During Early Anti-thrombotic Therapy After Bioprosthetic Aortic Valve Replacement

NCT ID: NCT00465218

Last Updated: 2012-06-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

56 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-03-31

Study Completion Date

2011-03-31

Brief Summary

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The purpose of this study is to determine if there is any difference in the counts of cerebral emboli and platelet function between two prophylactic treatments of thrombosis currently used at University of Ottawa Heart Institute for the first three months after surgery in low-risk patients undergoing aortic valve replacement with a bioprosthetic valve: 1) daily use of high-dose aspirin \[325 mgs\], and 2) the combination of oral Warfarin \[target INR 2.0 to 3.0\] and low-dose aspirin \[81 mg\].

Detailed Description

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Background:

There are several medications used to prevent blood clotting in patients undergoing surgical replacement of their aortic valves with tissue valves. One of these medications is called warfarin (Coumadin ®) which prevents blood clotting by making the blood "thinner." Another medication is aspirin which prevents the aggregation (clustering) of cells in the blood called platelets. Some clinicians consider that using only aspirin should be enough to protect the patients against the presence of clots in the blood, but others consider that aspirin should be combined with warfarin for better protection. Moreover, physicians express concern over the use of oral anticoagulation due to the possibility of an increased risk of bleeding. The effects of these medications for preventing blood clots traveling to the brain after the surgery are currently unknown. Transcranial doppler ultrasound will be used in these patients to evaluate non-invasively the quantity of fragments of clots circulating in the arteries of the brain. In addition, platelet function will be measured to determine how effective these treatments are for preventing the aggregation of the blood cells called platelets, which may be involved in clot formation.

Objective:

Our purpose is to determine if there is any difference in the counts of cerebral emboli and platelet function between two prophylactic treatments of thrombosis currently used in our institution for the first three months after surgery in these patients: 1) daily use of high-dose aspirin \[325 mgs\], and 2) the combination of oral Warfarin \[target INR 2.0 to 3.0\] and low-dose aspirin \[81 mg\].

Methods:

Patients with low risk profile undergoing primary aortic valve replacement with a bioprosthetic (tissue) valve will be eligible for the study. Patients will receive one of the two prophylactic treatments of thrombosis (1 or 2) depending on the surgeon's preference. Platelet function will be measured before surgery and transcranial doppler within the first 24 hours immediately after the surgery. At the end of one month following surgery, all patients will undergo transcranial doppler and platelet function assessment. The study will be powered on demonstrating the hypothesis of substantial equivalence between the two treatments as regarding the primary outcome (cerebral emboli).

Outcome measures:

1. Primary outcome:

Bilateral counts of cerebral emboli in the middle cerebral arteries with transcranial doppler ultrasound at one month after surgery
2. Secondary outcomes:

Platelet function, incidence of major adverse neurologic and bleeding events at one month following surgery

Conditions

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Aortic Valve Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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1

High dose aspirin (325 mg)

Prophylaxis of Thrombosis after aortic valve replacement

Intervention Type PROCEDURE

Two standard prophylactic treatments of thrombosis within the first 3 months postsurgery currently used in our institution: a) daily dose of aspirin (325 mgs; b) daily dose of aspirin (81 mg) plus Warfarin for target INR 2.0-2.5

2

Low dose aspirin (81 mgs) plus warfarin

Prophylaxis of Thrombosis after aortic valve replacement

Intervention Type PROCEDURE

Two standard prophylactic treatments of thrombosis within the first 3 months postsurgery currently used in our institution: a) daily dose of aspirin (325 mgs; b) daily dose of aspirin (81 mg) plus Warfarin for target INR 2.0-2.5

Interventions

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Prophylaxis of Thrombosis after aortic valve replacement

Two standard prophylactic treatments of thrombosis within the first 3 months postsurgery currently used in our institution: a) daily dose of aspirin (325 mgs; b) daily dose of aspirin (81 mg) plus Warfarin for target INR 2.0-2.5

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients undergoing primary aortic valve replacement with bioprosthetic (tissue) valve.

Exclusion Criteria

* Emergency surgery or redo operations.
* Patients with history of transient ischemic attacks, stroke, or history of carotid stenosis greater than 50% as detected by carotid duplex doppler or angiography.
* Patients with COPD who are CO2 retainers.
* Patients with LV function less than 50%, or enlarged left ventricle greater than 50 mm as detected by echocardiography or previous history of thromboembolism.
* Patients with history of atrial fibrillation or heart rhythm disturbances.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Edwards Lifesciences

INDUSTRY

Sponsor Role collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role lead

Responsible Party

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Marc Ruel MD MPH FRCSC

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marc Ruel, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Thierry Mesana, MD, PhD

Role: STUDY_DIRECTOR

Ottawa Heart Institute Research Corporation

Locations

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University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Countries

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Canada

References

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Gohlke-Barwolf C, Acar J, Oakley C, Butchart E, Burckhart D, Bodnar E, Hall R, Delahaye JP, Horstkotte D, Kremer R, et al. Guidelines for prevention of thromboembolic events in valvular heart disease. Study Group of the Working Group on Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 1995 Oct;16(10):1320-30. doi: 10.1093/oxfordjournals.eurheartj.a060739. No abstract available.

Reference Type BACKGROUND
PMID: 8746900 (View on PubMed)

ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association. Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). J Am Coll Cardiol. 1998 Nov;32(5):1486-588. doi: 10.1016/s0735-1097(98)00454-9. No abstract available.

Reference Type BACKGROUND
PMID: 9809971 (View on PubMed)

Stein PD, Alpert JS, Bussey HI, Dalen JE, Turpie AG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest. 2001 Jan;119(1 Suppl):220S-227S. doi: 10.1378/chest.119.1_suppl.220s.

Reference Type BACKGROUND
PMID: 11157651 (View on PubMed)

Kirtane AJ, Rahman AM, Martinezclark P, Jeremias A, Seto TB, Manning WJ. Adherence to American College of Cardiology/American Heart Association guidelines for the management of anticoagulation in patients with mechanical valves undergoing elective outpatient procedures. Am J Cardiol. 2006 Mar 15;97(6):891-3. doi: 10.1016/j.amjcard.2005.09.139. Epub 2006 Feb 2.

Reference Type BACKGROUND
PMID: 16516596 (View on PubMed)

Heras M, Chesebro JH, Fuster V, Penny WJ, Grill DE, Bailey KR, Danielson GK, Orszulak TA, Pluth JR, Puga FJ, et al. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol. 1995 Apr;25(5):1111-9. doi: 10.1016/0735-1097(94)00563-6.

Reference Type BACKGROUND
PMID: 7897124 (View on PubMed)

Moinuddeen K, Quin J, Shaw R, Dewar M, Tellides G, Kopf G, Elefteriades J. Anticoagulation is unnecessary after biological aortic valve replacement. Circulation. 1998 Nov 10;98(19 Suppl):II95-8; discussion II98-9.

Reference Type BACKGROUND
PMID: 9852888 (View on PubMed)

Gherli T, Colli A, Fragnito C, Nicolini F, Borrello B, Saccani S, D'Amico R, Beghi C. Comparing warfarin with aspirin after biological aortic valve replacement: a prospective study. Circulation. 2004 Aug 3;110(5):496-500. doi: 10.1161/01.cir.0000137122.95108.52.

Reference Type BACKGROUND
PMID: 15289387 (View on PubMed)

Rodriguez RA, Rubens F, Rodriguez CD, Nathan HJ. Sources of variability in the detection of cerebral emboli with transcranial Doppler during cardiac surgery. J Neuroimaging. 2006 Apr;16(2):126-32. doi: 10.1111/j.1552-6569.2006.00035.x.

Reference Type BACKGROUND
PMID: 16629734 (View on PubMed)

Zimmermann N, Roussiekan T, Winter J, Kurt M, Gams E, Wenzel F, Hohlfeld T. Platelet inhibition by aspirin after aortic valve replacement. J Thorac Cardiovasc Surg. 2006 Jun;131(6):1392-3. doi: 10.1016/j.jtcvs.2006.01.029. No abstract available.

Reference Type BACKGROUND
PMID: 16733175 (View on PubMed)

Geiser T, Sturzenegger M, Genewein U, Haeberli A, Beer JH. Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral microemboli, and platelet microparticles in patients with prosthetic heart valves. Stroke. 1998 Sep;29(9):1770-7. doi: 10.1161/01.str.29.9.1770.

Reference Type BACKGROUND
PMID: 9731593 (View on PubMed)

Sturzenegger M, Beer JH, Rihs F. Monitoring combined antithrombotic treatments in patients with prosthetic heart valves using transcranial Doppler and coagulation markers. Stroke. 1995 Jan;26(1):63-9. doi: 10.1161/01.str.26.1.63.

Reference Type BACKGROUND
PMID: 7839399 (View on PubMed)

Markus HS, Thomson ND, Brown MM. Asymptomatic cerebral embolic signals in symptomatic and asymptomatic carotid artery disease. Brain. 1995 Aug;118 ( Pt 4):1005-11. doi: 10.1093/brain/118.4.1005.

Reference Type BACKGROUND
PMID: 7655877 (View on PubMed)

Other Identifiers

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2006785-01H

Identifier Type: -

Identifier Source: org_study_id

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