The purpose of this study is to determine whether long-term treatment with a beta-blocker (BB) such as atenolol and/or an angiotensin receptor blocker (ARB) such as telmisartan, given to adult patients with bicuspid aortic valve (BAV) disease (aortopathy) reduces the widening (dilatation) of the aorta from its baseline size.
Bicuspid aortic valve (BAV) is the most common congenital heart disease lesion with an estimated 280 000 to 560 000 people affected in the Canada. Dilatation of the ascending aorta is a common feature in patients with BAV and is a result of inherent vascular abnormalities with superimposed effects of age and acquired cardiovascular risk factors. Severe aortic dilatation (\> 50mm) leads to aortic dissection and premature death. Histopathological studies of the aortas in patients with BAVs report similar findings to that of patients with Marfan syndrome. Beta Blocker (BB) therapy and more recently, Angiotensin Receptor Blocker (ARB) therapy, have been shown to decrease to rate of aortic dilatation and be of benefit to patients with Marfan syndrome. There is no such data however in patients with BAV and aortopathy. Within the context of a randomized clinical trial, the investigators proposed to test the hypothesis that BB or ARB will reduce the rate of progressive aortic dilatation in adults with BAVs and ascending aortopathy as compared to placebo. Design: Multicentre, randomized, double-blind, placebo-controlled, trial of adult patients with bicuspid aortic valve aortopathy. Patients who are eligible to take either study medication will be randomly allocated to participate in either the BB (atenolol) vs. placebo arm, or the ARB (telmisartan) vs. placebo arm. Patients who are ineligible for the BB arm will be assigned to the ARB vs. placebo arm and patients who are ineligible for the ARB arm will be assigned to the BB vs. placebo arm. Within each arm, all participants will be randomized to take either placebo or active medication. The atenolol arm will be up-titrated to100mg/day and the telmisartan arm will be up-titrated to 80 mg/day, or to the maximum tolerated dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
85
Atenolol or matching placebo 25 mg up-titrated to 100 mg
Telmisartan or matching placebo 40 mg up-titrated to 80mg.
Mazankowski Alberta Heart Institute
Edmonton, Alberta, Canada
University of British Columbia
Vancouver, British Columbia, Canada
St. Boniface Hospital
Winnipeg, Manitoba, Canada
Change From Baseline in Ascending Aorta Size, as Evaluated by MRI
The primary analyses include the evaluation of the effects of monotherapy (atenolol vs. placebo, telmisartan vs. placebo) on the change in aortic root size measured at 3 years. Change is measured in centimeters squared (final measurement - baseline measurement). Original outcome measure time frame was scheduled for 5 years, however due to poor study participant and site recruitment study was closed early and final outcome measures taken at approximately 3 years.
Time frame: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)
Rate of Change in Ascending Aorta Size Evaluated by Transthoracic Echocardiography (TEE)
Rate of change in ascending aorta size evaluated by transthoracic echocardiography (ECHO) at 3 years. Change is measured in centimeters squared (final measurement - baseline measurement). Time frame was scheduled for 5 years, however due to poor study participant and site recruitment study was closed early and final outcome measures taken at approximately 3 years.
Time frame: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)
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Hamilton Health Sciences-General
Hamilton, Ontario, Canada
Population Health Research Institute - Coordinating Centre
Hamilton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Toronto General Hospital/University of Toronto
Toronto, Ontario, Canada
Cité de la Santé de Laval
Laval, Quebec, Canada
McGill University Health Centre
Montreal, Quebec, Canada
...and 3 more locations