Clinical trial NCT00465218: Transcranial Doppler (TCD) Assessment During Early Anti-thrombotic Therapy After Bioprosthetic Aortic Valve Replacement
Official title: "Transcranial Doppler Assessment of Cerebral Embolization During Early Anti-thrombotic Therapy After Bioprosthetic Aortic Valve Replacement: Comparison of High-dose Aspirin Versus Warfarin Plus Low-dose Aspirin"
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aortic Valve Disease
Keywords: Bioprosthesis
Thrombosis
Cerebral emboli
Transcranial Doppler
Platelet function tests
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Edwards Lifesciences
First posted: 2007-04-24
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with aortic valve stenosis and/or insuficiency undergoing aortic valve replacement with a bioprosthetic valve (tissue valve).

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Differences in the rate of doppler-detected cerebral micro emboli between the two prophylactic treatments of thrombosis
timeFrame: 1 month after surgery
Secondary outcomes:
measure: Differences in the degree of inhibition of platelet aggregation between the two prophylactic treatments of thrombosis
timeFrame: 1 month after surgery
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Marc Ruel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Thierry Mesana, MD, PhD
role: STUDY_DIRECTOR
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