Effect of Bisoprolol on Progression of Aortic Stenosis

NCT01579058 | Terminated Phase 4 DMC

• 1 other identifier: 2011-0884
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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.

Conditions

Aortic Stenosis

Keywords

aortic stenosis; beta-blocker

Outcome Measures

Primary Outcomes (1)

• Change in peak aortic jet velocity from baseline to 4 years follow-up

  Change in peak aortic jet velocity from baseline to 4 years follow-up. For each patient, the change in peak aortic jet velocity is calculated as (peak aortic jet velocity at 4 year follow-up) - (peak aortic jet velocity at baseline) on Doppler echocardiography.

  4 years

Secondary Outcomes (4)

• Change in mean pressure gradient across aortic valve

  4 years

• Change in aortic valve area

  4 years

• Change in BNP levels

  4 years

• Change in E/E' ratio

  4 years

Study Arms (2)

bisoprolol

ACTIVE COMPARATOR

bisoprolol 5mg qd

Drug: bisoprolol

placebo

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

bisoprolol DRUG

bisoprolol 5mg qd for 4 years

Also known as: Concor

bisoprolol

placebo DRUG

placebo for 4 years

placebo

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Duk-Hyun Kang, M.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 14, 2012
• First Posted: April 17, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 27, 2018

Record last verified: 2018-06

Locations

KR (3)