Cardiac DiseasePhase 3BAVNCT01202721
Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
A Phase 3 study testing Atenolol and Telmisartan in people with Cardiac Disease, run by Hamilton Health Sciences Corporation at 13 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Disease
- What is being tested?
- Atenolol and Telmisartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 13 sitesCanada
- Study dates
- Jun 2011to Nov 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 32Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Canada13 sites
Mazankowski Alberta Heart Institute
Edmonton, Alberta, T6G 2B7
Hamilton Health Sciences-General
Hamilton, Ontario, L8L 2X2
Population Health Research Institute - Coordinating Centre
Hamilton, Ontario, L8L2X2
Cité de la Santé de Laval
Laval, Quebec, H7M 3L9
London Health Sciences Centre
London, Ontario, N6A 5A5
McGill University Health Centre
Montreal, Quebec, H3A 1A1
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Regina General Hospital
Regina, Saskatchewan, S4P 0W5
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Toronto General Hospital/University of Toronto
Toronto, Ontario
University of British Columbia
Vancouver, British Columbia, V6Z 1Y6
St. Boniface Hospital
Winnipeg, Manitoba
About this study
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.
Read the 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.
- Conditions
- Cardiac Disease
- Being tested
- Atenolol, Telmisartan
- Keywords
- Congenital, Aortic Valve, Bicuspid, Aortopathy, bicuspid aortic valve aortopathy
- Medical subject headings
- Heart Diseases, Bicuspid Aortic Valve Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtenololDrug
Also called Atenolol 25/50/100 mg, or matched placebo
Atenolol or matching placebo 25 mg up-titrated to 100 mg
TelmisartanDrug
Also called Micardis 40/80 mg, or matched placebo
Telmisartan or matching placebo 40 mg up-titrated to 80mg.
| Study group | Role | What they receive |
|---|---|---|
| Atenolol | Experimental | Atenolol or matching placebo 25 mg up-titrated to 100 mg. Receives: Drug: Atenolol |
| Telmisartan | Experimental | Telmisartan or matching placebo 40 mg up-titrated to 80mg Receives: Drug: Telmisartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)
Secondary outcomes (1)
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.
Measured: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startJun 2011
- Primary completion19 Apr 2016
- Study completionNov 2016
Why it stopped: Terminated early due to lack of study feasibility and poor patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiac DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- Population Health Research Institute
- Responsible party
- Sponsor
- Investigators
- Judith Therrien, MD, Principal investigator, MdGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01202721
- Sponsor's protocol ID
- BAV-15JUNE2010
- Acronym
- BAV
- Status last verified
- Aug 2019
- First submitted
- 14 Sep 2010
- Last updated
- 18 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
- ClinicalTrials.gov ID
- NCT01202721
- Acronym / sponsor ID
- BAV / BAV-15JUNE2010
- Conditions
- Cardiac Disease
- Keywords
- Congenital, Aortic Valve, Bicuspid, Aortopathy, bicuspid aortic valve aortopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated early due to lack of study feasibility and poor patient recruitment
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Collaborators
- Population Health Research Institute
- Study start
- Jun 2011 (actual)
- Primary completion
- 19 Apr 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 16 Sep 2010 (estimated)
- Results
- Posted 18 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atenolol | Experimental | Drug: AtenololAtenolol or matching placebo 25 mg up-titrated to 100 mg. |
| Telmisartan | Experimental | Drug: TelmisartanTelmisartan or matching placebo 40 mg up-titrated to 80mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtenololAlso: Atenolol 25/50/100 mg, or matched placeboAtenolol or matching placebo 25 mg up-titrated to 100 mg | Drug | Atenolol |
| TelmisartanAlso: Micardis 40/80 mg, or matched placeboTelmisartan or matching placebo 40 mg up-titrated to 80mg. | Drug | Telmisartan |
Primary outcome
Change From Baseline in Ascending Aorta Size, as Evaluated by MRI
Time frame: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)
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.
1 secondary outcome
Rate of Change in Ascending Aorta Size Evaluated by Transthoracic Echocardiography (TEE)
Time frame: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cardiac Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
RecruitingObservational study
AI-powered ECG Analysis Using Willem™ Software in High-risk Cardiac Patients (WILLEM)
Cardiomyopathies, Cardiac Arrest
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith Therrien, MD principal investigator
MdGill University
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atenolol and Telmisartan in people with Cardiac Disease, run by Hamilton Health Sciences Corporation at 13 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Ascending Aorta Size, as Evaluated by MRI (time frame: The difference between baseline measures (2012-2013) and Year 3 measure (2015-2016)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2019.