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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Hamilton Health Sciences Corporation
Sponsor:
Collaborator:
Population Health Research Institute
Information provided by (Responsible Party):
Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier:
NCT01202721
First received: September 14, 2010
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Cardiac Disease
Drug: Atenolol
Drug: Telmisartan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)

Resource links provided by NLM:


Further study details as provided by Hamilton Health Sciences Corporation:

Primary Outcome Measures:
  • Change from baseline in ascending aorta size, as evaluated by MRI [ Time Frame: Baseline, Year 3, Year 5 ] [ Designated as safety issue: No ]
    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 baseline, 3 years and 5 years.


Secondary Outcome Measures:
  • Rate of change in ascending aorta size evaluated by transthoracic echocardiography (TEE). [ Time Frame: Baseline, Year 1, year 2, Year 3, Year 4 and Final ] [ Designated as safety issue: No ]

Estimated Enrollment: 416
Study Start Date: June 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atenolol
Atenolol or matching placebo 25 mg up-titrated to 100 mg.
Drug: Atenolol
Atenolol or matching placebo 25 mg up-titrated to 100 mg
Other Names:
  • Atenolol 25/50/100 mg
  • or matched placebo
Experimental: Telmisartan
Telmisartan or matching placebo 40 mg up-titrated to 80mg
Drug: Telmisartan
Telmisartan or matching placebo 40 mg up-titrated to 80mg.
Other Names:
  • Micardis 40/80 mg
  • or matched placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01202721

Contacts
Contact: Tara McCready, PhD 905-527-4322 ext 40439 tara.mccready@phri.ca
Contact: Parvez Khatib 905-527-4322 ext 40550 parvez.khatib@phri.ca

Locations
Canada, Alberta
Mazankowski Alberta Heart Institute Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Principal Investigator: Isabelle VonderMuhll         
Canada, British Columbia
University of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Principal Investigator: Jasmine Grewal         
Canada, Manitoba
St. Boniface Hospital Recruiting
Winnipeg, Manitoba, Canada
Principal Investigator: James Tam         
Canada, Ontario
Population Health Research Institute - Coordinating Centre Active, not recruiting
Hamilton, Ontario, Canada, L8L2X2
Hamilton Health Sciences-General Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Principal Investigator: Omid Salehian         
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 5A5
Principal Investigator: Samuel Siu         
Toronto General Hospital/University of Toronto Recruiting
Toronto, Ontario, Canada
Principal Investigator: Candice Silversides         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Principal Investigator: Michael Kutryk, MD         
Canada, Quebec
Cité de la Santé de Laval Recruiting
Laval, Quebec, Canada, H7M 3L9
Principal Investigator: Laurence Descarries, MD         
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Principal Investigator: Judith Therrien         
McGill University Health Centre Recruiting
Montreal, Quebec, Canada, H3A 1A1
Principal Investigator: Judith Therrien         
Canada, Saskatchewan
Regina General Hospital Recruiting
Regina, Saskatchewan, Canada, S4P 0W5
Principal Investigator: Payam Dehghani, MD         
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Population Health Research Institute
Investigators
Principal Investigator: Judith Therrien, MD MdGill University
  More Information

No publications provided

Responsible Party: Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01202721     History of Changes
Other Study ID Numbers: BAV-15JUNE2010
Study First Received: September 14, 2010
Last Updated: May 26, 2014
Health Authority: Canada: Health Canada

Keywords provided by Hamilton Health Sciences Corporation:
Congenital
Aortic Valve
Bicuspid
Aortopathy
bicuspid aortic valve aortopathy

Additional relevant MeSH terms:
Heart Diseases
Aortic Valve Stenosis
Heart Valve Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Ventricular Outflow Obstruction
Cardiovascular Abnormalities
Congenital Abnormalities
Adrenergic beta-Antagonists
Atenolol
Telmisartan
Angiotensin Receptor Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Angiotensin II Type 1 Receptor Blockers

ClinicalTrials.gov processed this record on September 11, 2014