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Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study) (BAV)

Primary Purpose

Cardiac Disease

Status
Terminated
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Atenolol
Telmisartan
Sponsored by
Hamilton Health Sciences Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cardiac Disease focused on measuring Congenital, Aortic Valve, Bicuspid, Aortopathy, bicuspid aortic valve aortopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mazankowski Alberta Heart Institute
  • University of British Columbia
  • St. Boniface Hospital
  • Hamilton Health Sciences-General
  • Population Health Research Institute - Coordinating Centre
  • London Health Sciences Centre
  • St. Michael's Hospital
  • Toronto General Hospital/University of Toronto
  • Cité de la Santé de Laval
  • McGill University Health Centre
  • Jewish General Hospital
  • Centre Hospitalier Universitaire de Sherbrooke
  • Regina General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Atenolol

Telmisartan

Arm Description

Atenolol or matching placebo 25 mg up-titrated to 100 mg.

Telmisartan or matching placebo 40 mg up-titrated to 80mg

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
September 14, 2010
Last Updated
August 12, 2019
Sponsor
Hamilton Health Sciences Corporation
Collaborators
Population Health Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01202721
Brief Title
Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
Acronym
BAV
Official Title
Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
Terminated early due to lack of study feasibility and poor patient recruitment
Study Start Date
June 2011 (Actual)
Primary Completion Date
April 19, 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hamilton Health Sciences Corporation
Collaborators
Population Health Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Disease
Keywords
Congenital, Aortic Valve, Bicuspid, Aortopathy, bicuspid aortic valve aortopathy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
85 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atenolol
Arm Type
Experimental
Arm Description
Atenolol or matching placebo 25 mg up-titrated to 100 mg.
Arm Title
Telmisartan
Arm Type
Experimental
Arm Description
Telmisartan or matching placebo 40 mg up-titrated to 80mg
Intervention Type
Drug
Intervention Name(s)
Atenolol
Other Intervention Name(s)
Atenolol 25/50/100 mg, or matched placebo
Intervention Description
Atenolol or matching placebo 25 mg up-titrated to 100 mg
Intervention Type
Drug
Intervention Name(s)
Telmisartan
Other Intervention Name(s)
Micardis 40/80 mg, or matched placebo
Intervention Description
Telmisartan or matching placebo 40 mg up-titrated to 80mg.
Primary Outcome Measure Information:
Title
Change From Baseline in Ascending Aorta Size, as Evaluated by MRI
Description
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)
Secondary Outcome Measure Information:
Title
Rate of Change in Ascending Aorta Size Evaluated by Transthoracic Echocardiography (TEE)
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age => 18 years Men and women with BAV and ascending aorta measuring > 37mm. Written informed consent General Study Exclusion Criteria 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 Systolic blood pressure < 100 mmHg 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. Ascending aorta measuring ≥ 50mm, requiring prophylactic ascending aorta surgery Unable to provide informed consent 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. Prior surgery on ascending aorta or aortic root (balloon valvuloplasty, aortic valvotomy or post coarctation surgery are acceptable) Women who are pregnant at screening visit Contraindication to MRI (claustrophobia, pacemaker, metallic clip in eye or brain) History of any illness which limits the participants' ability to complete the study Additional Exclusion Criteria for BB arm only Heart rate <60 bpm Heart block (1st, 2nd and 3rd degree AV block on ECG), or sick sinus syndrome Asthma of sufficient severity to represent a contraindication to BB use in the judgment of the patient's physician History of severe peripheral artery disorders History of pheochromocytoma without the use of alpha-adrenergic blockers History of metabolic acidosis Additional Exclusion Criteria for ARB arm only Women who are pregnant, lactating or who intend to become pregnant during the course of the study Women who are of childbearing age and are not on reliable, accepted form of birth control Hyperkalemia [serum potassium > 5.5 mmol/L] or renal dysfunction [GFR<45% measured by MDRD) 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.) History of bilateral renal artery stenosis or unilateral renal artery stenosis to a solitary kidney History of hepatic insufficiency and hepato-biliary obstruction History of fructose intolerance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Therrien, MD
Organizational Affiliation
MdGill University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mazankowski Alberta Heart Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
St. Boniface Hospital
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
Hamilton Health Sciences-General
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Facility Name
Population Health Research Institute - Coordinating Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L2X2
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
Toronto General Hospital/University of Toronto
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Cité de la Santé de Laval
City
Laval
State/Province
Quebec
ZIP/Postal Code
H7M 3L9
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Centre Hospitalier Universitaire de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Regina General Hospital
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
S4P 0W5
Country
Canada

12. IPD Sharing Statement

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Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)

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