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

NCT ID: NCT01202721

Last Updated: 2019-09-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2016-11-30

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.

Conditions

Cardiac Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Atenolol

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

Group Type: EXPERIMENTAL

Atenolol

Intervention Type: DRUG

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

Telmisartan

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

Group Type: EXPERIMENTAL

Telmisartan

Intervention Type: DRUG

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

Interventions

Atenolol

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

Intervention Type: DRUG

Telmisartan

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

Intervention Type: DRUG

Other Intervention Names

Atenolol 25/50/100 mg; or matched placebo; Micardis 40/80 mg; or matched placebo

Eligibility Criteria

Inclusion Criteria

• Age => 18 years
• Men and women with BAV and ascending aorta measuring > 37mm.
• Written informed consent

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

4. Ascending aorta measuring ≥ 50mm, requiring prophylactic ascending aorta surgery

5. Unable to provide informed consent

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

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

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Population Health Research Institute

OTHER

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Therrien, MD

Role: PRINCIPAL_INVESTIGATOR

MdGill University

Locations

Mazankowski Alberta Heart Institute

Edmonton, Alberta, Canada

University of British Columbia

Vancouver, British Columbia, Canada

St. Boniface Hospital

Winnipeg, Manitoba, Canada

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

Jewish General Hospital

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Regina General Hospital

Regina, Saskatchewan, Canada

Countries

Canada

Other Identifiers

BAV-15JUNE2010

Identifier Type: -

Identifier Source: org_study_id