Angiotensin-II Blockade in Mitral Regurgitation

This study has been completed.
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00587470
First received: December 21, 2007
Last updated: October 14, 2010
Last verified: October 2010

December 21, 2007
October 14, 2010
August 1998
August 2001   (final data collection date for primary outcome measure)
Tolerance of the medication. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00587470 on ClinicalTrials.gov Archive Site
Decrease of severity of mitral regurgitation. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Angiotensin-II Blockade in Mitral Regurgitation
Angiotensin-II Blockade in Mitral Regurgitation

Mitral regurgitation (MR) is common in the elderly and its prevalence is increasing with the aging of the population. Organic MR, due to primary valvular lesions, initiates a cascade of complications determined by its degree. MR of severe degree is associated with excess mortality and high cardiac morbidity (heart failure, atrial fibrillation). It also causes left ventricular remodeling which induces left ventricular dysfunction, which in turn leads to poor clinical outcome. Surgery can eliminate MR, but carries immediate and long-term risks, especially in the elderly. Therefore, chronically decreasing the degree of MR is a major goal of medical therapy but such an effect is yet unproved because of conflicting results of small and mostly non-randomized series. Our recent preliminary studies suggest that a sustained decrease of degree of MR and improvement of left ventricular remodeling can be achieved with powerful reduction of afterload, obtained in particular with angiotensin-II receptor blockade. Therefore, the present proposal seeks to address gaps of knowledge regarding vasoactive treatment of MR through the verification of the following hypothesis: Hypothesis: Vasoactive therapy using angiotensin-II receptor blocker (Candesartan Cilexetil) weighed against placebo produces a sustained reduction of the consequences of organic MR. The specific aims are that the treatment a) decreases the degree of MR (decreases the regurgitant volume, primary end-point) and b) improves left ventricular remodeling (decreases the end-diastolic volume index, secondary end-point), as compared to placebo.

Patients with MR organic (intrinsic valve disease), isolated (no other valve disease), moderate or more severe (regurgitant volume *30 mL/beat). A Clinical trial, randomized, placebo controlled, double-blind, without cross-over, of 1 year oral treatment with potent angiotensin-II receptor blockade using 32 mg Candesartan daily. The trial is preceded in all patients by an acute open-label study to determine tolerance and immediate response. The methods used to measure the end-points will be: a) Doppler-Echocardiography for quantitation of the degree of MR (measurement of regurgitant volume) using a combination of three simultaneous methods (quantitative Doppler, quantitative two-dimensional echocardiography, proximal flow convergence) and b) of left ventricular remodeling (end-diastolic volume index measured by echocardiography and by electron beam computed tomography). This single center study seeks to enroll a total of 90 patients. The analysis will be based on intention to treat and compare the regurgitant volume and left ventricular end-diastolic volume index measured after one year of treatment with the active drug or placebo. The results of the trial should provide strong evidence regarding medical treatment of patients with organic MR.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Mitral Regurgitation
  • Drug: Candesartan
    Maximum vasodilation.
    Other Name: atacand
  • Drug: atacand
    maximum vasodilation
    Other Name: candesartan
  • Drug: Placebo
    Placebo
  • Experimental: 1
    Atacand treatment.
    Interventions:
    • Drug: Candesartan
    • Drug: atacand
  • Placebo Comparator: 2
    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.
 
Completed
60
August 2001
August 2001   (final data collection date for primary outcome measure)

Inclusion Criteria:

Patients:

  • 18 years old or older, with
  • Mitral regurgitation on the basis of Color flow imaging
  • Due to organic disease of the mitral valve on the basis of two-dimensional echocardiography
  • Isolated (no valve disease other than functional tricuspid regurgitation on the basis of Doppler-Echocardiography)
  • Pure (no mitral stenosis by Doppler echocardiography)
  • Quantifiable by Doppler-Echocardiographic methods
  • Of more than mild degree, defined as regurgitant volume * 30 mL/beat
  • Occurring on native valves
  • With Two-dimensional echocardiographic imaging allowing assessment of LV remodeling, and
  • Asymptomatic (or mildly symptomatic but not considered as candidates for immediate surgery by their attending physician).

Exclusion Criteria:

  • Associated aortic valve disease (more than trace aortic regurgitation by color flow imaging or mean gradient *25 mmHg)
  • Associated mitral stenosis (mean gradient* 5 mmHg, valve area < 1.5 cm2)
  • Associated congenital or pericardial diseases on the basis of Doppler echocardiography
  • Intolerance to either AII blockers or Angiotensin converting enzyme inhibitors
  • Intolerance to iodine contrast material
  • Intolerance to intravenous echographic contrast agents
  • Renal failure with creatinine * 2 mg/dl
  • Blood pressure below 100 mmHg
  • Known renal artery stenosis
  • Ongoing therapy with hydralazine, calcium-entry blocking drugs or angiotensin converting enzyme inhibitors
  • Known severe comorbidity such as liver disease, malignancy
  • Pregnancy (A negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential (not post-menopausal or surgically sterilized)), and
  • Patients considered as requiring mitral valve surgery by their attending physician or with previous valve repair or replacement.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00587470
1129-98
Yes
Maurice Enriquez-Sarano M.D., Mayo Clinic Foundation
Mayo Clinic
Not Provided
Principal Investigator: Maurice E. Sarano, M.D. Mayo Clinic Foundation
Mayo Clinic
October 2010

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