Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
Information source: Hamilton Health Sciences Corporation
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiac Disease
Intervention: Atenolol (Drug); Telmisartan (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Hamilton Health Sciences Corporation Official(s) and/or principal investigator(s): Judith Therrien, MD, Principal Investigator, Affiliation: MdGill University
Overall contact: Tara McCready, PhD, Phone: 905-527-4322, Ext: 40439, Email: tara.mccready@phri.ca
Summary
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.
Clinical Details
Official title: Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Change from baseline in ascending aorta size, as evaluated by MRI
Secondary outcome: Rate of change in ascending aorta size evaluated by transthoracic echocardiography (TEE).
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age => 18 years
- Men and women with BAV and ascending aorta measuring > 37mm.
- Written informed consent
General Study Exclusion Criteria
1. History of cardiac diseases, such as
- Symptomatic aortic stenosis or aortic regurgitation referred for surgical
intervention or asymptomatic severe aortic stenosis or regurgitation based on
current guidelines
- Uncontrolled heart failure, right ventricular failure due to pulmonary
hypertension
- Cardiogenic shock
2. Systolic blood pressure < 100 mmHg
3. History of drug sensitivity, contraindication or adverse reaction to both BB and ARB.
Participants who are able to tolerate only a BB will be allocated to the BB vs.
placebo arm, and participants who are able to tolerate only an ARB will be allocated
to the ARB vs. placebo arm, assuming no other exclusion criteria are met.
4. Ascending aorta measuring ≥ 50mm, requiring prophylactic ascending aorta surgery
5. Unable to provide informed consent
6. Need for both BB and ARB for treatment of concomitant medical conditions for which
there are no other alternatives. Participants who are taking an ARB which cannot be
discontinued will be allocated to the BB arm, and participants who are taking a BB
which cannot be discontinued will be allocated to the ARB arm, if no other exclusion
criteria are met.
7. Prior surgery on ascending aorta or aortic root (balloon valvuloplasty, aortic
valvotomy or post coarctation surgery are acceptable)
8. Women who are pregnant at screening visit
9. Contraindication to MRI (claustrophobia, pacemaker, metallic clip in eye or brain)
10. History of any illness which limits the participants' ability to complete the study
Additional Exclusion Criteria for BB arm only
1. Heart rate <60 bpm
2. Heart block (1st, 2nd and 3rd degree AV block on ECG), or sick sinus syndrome
3. Asthma of sufficient severity to represent a contraindication to BB use in the
judgment of the patient's physician
4. History of severe peripheral artery disorders
5. History of pheochromocytoma without the use of alpha-adrenergic blockers
6. History of metabolic acidosis
Additional Exclusion Criteria for ARB arm only
1. Women who are pregnant, lactating or who intend to become pregnant during the course
of the study
2. Women who are of childbearing age and are not on reliable, accepted form of birth
control
3. Hyperkalemia [serum potassium > 5. 5 mmol/L] or renal dysfunction [GFR<45% measured by
MDRD)
4. Patients being treated with an ACE Inhibitor that cannot be discontinued. (These
patients may be randomized in the BB arm if no exclusion criteria are met.)
5. History of bilateral renal artery stenosis or unilateral renal artery stenosis to a
solitary kidney
6. History of hepatic insufficiency and hepato-biliary obstruction
7. History of fructose intolerance
Locations and Contacts
Tara McCready, PhD, Phone: 905-527-4322, Ext: 40439, Email: tara.mccready@phri.ca
Mazankowski Alberta Heart Institute, Edmonton, Alberta T6G 2B7, Canada; Recruiting Isabelle VonderMuhll, Principal Investigator
University of British Columbia, Vancouver, British Columbia V6Z 1Y6, Canada; Recruiting Jasmine Grewal, Principal Investigator
St. Boniface Hospital, Winnipeg, Manitoba, Canada; Recruiting James Tam, Principal Investigator
Hamilton Health Sciences-General, Hamilton, Ontario L8L 2X2, Canada; Recruiting Omid Salehian, Principal Investigator
Population Health Research Institute - Coordinating Centre, Hamilton, Ontario L8L2X2, Canada; Active, not recruiting
London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Recruiting Samuel Siu, Principal Investigator
St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada; Recruiting Michael Kutryk, MD, Principal Investigator
Toronto General Hospital/University of Toronto, Toronto, Ontario, Canada; Recruiting Candice Silversides, Principal Investigator
Cité de la Santé de Laval, Laval, Quebec H7M 3L9, Canada; Recruiting Laurence Descarries, MD, Principal Investigator
Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada; Recruiting Judith Therrien, Principal Investigator
McGill University Health Centre, Montreal, Quebec H3A 1A1, Canada; Recruiting Judith Therrien, Principal Investigator
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada; Recruiting Hoa Do, MD, Principal Investigator
Regina General Hospital, Regina, Saskatchewan S4P 0W5, Canada; Recruiting Payam Dehghani, MD, Principal Investigator
Additional Information
Starting date: June 2011
Last updated: July 6, 2015
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