Effect of Bisoprolol on Progression of Aortic Stenosis

NCT ID: NCT01579058

Last Updated: 2018-06-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2014-05-31

Brief Summary

Aortic stenosis has been thought to be a degenerative process basically induced by long-lasting mechanical stress, and hemodynamic factors such as shear forces, acceleration of blood flow, hypertension and rapid heart rate might contribute to progression of aortic stenosis. Peak aortic jet velocity is known to be associated with clinical outcomes in mild and moderate AS, and our previous study showed that rate of progression was significantly associated with baseline aortic jet velocity in mild aortic stenosis. Because beta-blocker therapy would decrease aortic jet velocity and heart rate, it might decrease hemodynamic stress and eventually slow down the degenerative process in patients whose disease is not too advanced for therapy to be effective. The investigators hypothesized that a beta-blocker therapy would decrease the rate of progression of aortic stenosis by modifying hemodynamic factors favorably in patients with mild to moderate aortic stenosis.

Detailed Description

Aortic stenosis (AS) is a gradually progressive disease, characterized by an increase in calcium deposition leading to progressive narrowing of the aortic valve (AV). There are currently no effective medical treatment to halt the disease process and surgical valve replacement remains the only proven therapy when the valve becomes severely stenotic. AS is mediated by a chronic inflammatory disease process, very similar to that seen in atherosclerosis, but lipid-lowering therapy did not slow the progression of AS in the SALTIRE, SEAS, or ASTRONOMER trials. It is possible that these trials may have targeted patients in whom disease was too advanced for lipid-lowering therapy to be effective, or in whom atherosclerotic mechanism was not the central pathogenic process in AS. Because identifying and treating patients in earlier stages of AS would not be cost-effective, it seems more logical to explore alternative pharmacological approaches.

AS has been thought to be a degenerative process basically induced by long-lasting mechanical stress, and hemodynamic factors such as shear forces, acceleration of blood flow, hypertension and rapid heart rate might contribute to progression of AS. Peak aortic jet velocity is known to be associated with clinical outcomes in mild and moderate AS, and our previous study showed that rate of progression was significantly associated with baseline aortic jet velocity in mild AS. Because beta-blocker therapy would decrease aortic jet velocity and heart rate, it might decrease hemodynamic stress and eventually slow down the degenerative process in patients whose disease is not too advanced for therapy to be effective. In a retrospective, observational study, beta-blocker therapy was associated with a favorable clinical outcome in AS.

The investigators hypothesized that bisoprolol, a new generation beta-blocker, would decrease the rate of progression of AS by modifying hemodynamic factors favorably in patients with mild to moderate AS.

Conditions

Aortic Stenosis

Study Design

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

Study Groups

bisoprolol

bisoprolol 5mg qd

Group Type: ACTIVE_COMPARATOR

bisoprolol

Intervention Type: DRUG

bisoprolol 5mg qd for 4 years

placebo

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo for 4 years

Interventions

bisoprolol

bisoprolol 5mg qd for 4 years

Intervention Type: DRUG

placebo

placebo for 4 years

Intervention Type: DRUG

Other Intervention Names

Concor

Eligibility Criteria

Inclusion Criteria

• Mild to moderate aortic stenosis defined by peak velocity of aortic jet between 2.0 and 3.5 m/sec
• Untreated hypertension: systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg Treated hypertension using dihydropiridine calcium channel blockers, ACE inhibitors, ARB or diuretics
• Patients received no beta-blocker therapy for more than 12 months

Exclusion Criteria

• Symtomatic aortic stenosis: presence of exertional dyspnea, angina or syncope
• Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy) or planned major non-cardiac surgery within the study period
• Stroke or resuscitated sudden death in the past 6 months
• Evidence of congestive heart failure, or left ventricular ejection fraction < 50%
• Significant renal disease manifested by serum creatinine > 2.0mg/dL
• History of intolerance to beta-blocker
• History of adult asthma manifested by bronchospasm in the past 6 months, or currently taking regular anti-asthmatic medication(s)
• Moderate or severe aortic regurgitation
• Atrial fibrillation
• Female of child-bearing potential who do not use adequate contraception and women who are pregnant or breast-feeding
• A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer
• Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study
• Unwillingness or inability to comply with the procedures described in this protocol

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Duk-Hyun Kang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Duk-Hyun Kang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

2011-0884

Identifier Type: -

Identifier Source: org_study_id