Angiotensin-II Blockade in Mitral Regurgitation

NCT00587470 | Completed Phase 4 DMC

• 1 other identifier: 1129-98
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mitral Regurgitation

Keywords

valve, mitral, regurgitation

Outcome Measures

Primary Outcomes (1)

• Tolerance of the medication.

  one year

Secondary Outcomes (1)

• Decrease of severity of mitral regurgitation.

  1 year

Study Arms (2)

1

EXPERIMENTAL

Atacand treatment.

Drug: Candesartan; Drug: atacand

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Candesartan DRUG

Maximum vasodilation.

Also known as: atacand

1

atacand DRUG

maximum vasodilation

Also known as: candesartan

1

Placebo DRUG

Placebo

2

Eligibility Criteria

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

You may qualify if:

• Patients:
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905', United States

Location

MeSH Terms

Conditions

Mitral Valve Insufficiency

Interventions

candesartan; candesartan cilexetil

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Maurice E. Sarano, M.D.

  Mayo Clinic Foundation

  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

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 7, 2008
• Study Start: August 1, 1998
• Primary Completion: August 1, 2001
• Study Completion: August 1, 2001
• Last Updated: October 15, 2010

Record last verified: 2010-10

Locations

US (1)