Angiotensin-II Blockade in Mitral Regurgitation - Full Text View

Sponsor:	Mayo Clinic
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00587470

Purpose

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.

Condition	Intervention	Phase
Mitral Regurgitation	Drug: Candesartan Drug: atacand Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety Study
Official Title:	Angiotensin-II Blockade in Mitral Regurgitation

Resource links provided by NLM:

Drug Information available for: Angiotensin II CV 11974 Candesartan cilexetil Angiotensin II, ile(5)-

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Tolerance of the medication. [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Decrease of severity of mitral regurgitation. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	August 1998
Study Completion Date:	August 2001
Primary Completion Date:	August 2001 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Atacand treatment.	Drug: Candesartan Maximum vasodilation. Drug: atacand maximum vasodilation
2: Placebo Comparator Placebo	Drug: Placebo Placebo

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00587470

Locations

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905`

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:

Maurice E. Sarano, M.D.

Mayo Clinic Foundation

More Information

No publications provided

Responsible Party:	Mayo Clinic Foundation ( Maurice Enriquez-Sarano M.D. )
Study ID Numbers:	1129-98
Study First Received:	December 21, 2007
Last Updated:	June 4, 2008
ClinicalTrials.gov Identifier:	NCT00587470 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mayo Clinic:

valve, mitral, regurgitation

Additional relevant MeSH terms:

Heart Diseases
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Angiotensin II
Antihypertensive Agents
Pharmacologic Actions
Heart Valve Diseases

Candesartan cilexetil
Angiotensin II Type 1 Receptor Blockers
Therapeutic Uses
Candesartan
Vasoconstrictor Agents
Cardiovascular Diseases
Mitral Valve Insufficiency

ClinicalTrials.gov processed this record on February 08, 2010