Effect of Bisoprolol on Progression of Aortic Stenosis (BLAST)

This study is currently recruiting participants.
Verified October 2012 by Asan Medical Center
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Duk-Hyun Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01579058
First received: April 14, 2012
Last updated: October 21, 2012
Last verified: October 2012

April 14, 2012
October 21, 2012
July 2012
July 2018   (final data collection date for primary outcome measure)
Change in peak aortic jet velocity from baseline to 4 years follow-up [ Time Frame: 4 years ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01579058 on ClinicalTrials.gov Archive Site
  • Change in mean pressure gradient across aortic valve [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Change in mean pressure gradient across aortic valve from baseline to 4 years follow-up
  • Change in aortic valve area [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Change in aortic valve area from baseline to 4 years follow-up
  • Change in BNP levels [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Change in BNP levels from baseline to 4 years follow-up
  • Change in E/E' ratio [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Change in the ratio of E velocity (early mitral inflow velocity) to E' velocity (early mitral annular velocity) from baseline to 4 years follow-up
  • Change in mean pressure gradient across aortic valve [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Change in mean pressure gradient across aortic valve from baseline to 4 years follow-up
  • Change in aortic valve area [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Change in aortic valve area from baseline to 4 years follow-up
Not Provided
Not Provided
 
Effect of Bisoprolol on Progression of Aortic Stenosis
A Randomized Trial of Beta-blocker Therapy in Aortic Stenosis

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Aortic Stenosis
  • Drug: bisoprolol
    bisoprolol 5mg qd for 4 years
    Other Name: Concor
  • Drug: placebo
    placebo for 4 years
  • Active Comparator: bisoprolol
    bisoprolol 5mg qd
    Intervention: Drug: bisoprolol
  • Placebo Comparator: placebo
    placebo
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
July 2018
July 2018   (final data collection date for primary outcome measure)

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
Both
20 Years to 70 Years
No
Contact: Duk-Hyun Kang, M.D. 82-2-3010-3166 dhkang@amc.seoul.kr
Contact: Dae-Hee Kim, M.D. 82-2-3110-3151 daehee74@amc.seoul.kr
Korea, Republic of
 
NCT01579058
2011-0884
Yes
Duk-Hyun Kang, Asan Medical Center
Asan Medical Center
Merck Sharp & Dohme Corp.
Principal Investigator: Duk-Hyun Kang, M.D. Asan Medical Center
Asan Medical Center
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP