Back to results

Angiotensin-II Blockade in Mitral Regurgitation

Primary Purpose

Mitral Regurgitation

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Candesartan

atacand

Placebo

About this trial

This is an interventional treatment trial for Mitral Regurgitation focused on measuring valve, mitral, regurgitation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Atacand treatment.

Placebo

Outcomes

Primary Outcome Measures

Tolerance of the medication.

Secondary Outcome Measures

Decrease of severity of mitral regurgitation.

Full Information

NCT ID

NCT00587470

First Posted

December 21, 2007

Last Updated

October 14, 2010

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT00587470

Brief Title

Angiotensin-II Blockade in Mitral Regurgitation

Official Title

Angiotensin-II Blockade in Mitral Regurgitation

Study Type

Interventional

2. Study Status

Record Verification Date

October 2010

Overall Recruitment Status

Completed

Study Start Date

August 1998 (undefined)

Primary Completion Date

August 2001 (Actual)

Study Completion Date

August 2001 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Mayo Clinic

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mitral Regurgitation

Keywords

valve, mitral, regurgitation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Atacand treatment.

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Candesartan

Other Intervention Name(s)

atacand

Intervention Description

Maximum vasodilation.

Intervention Type

Drug

Intervention Name(s)

atacand

Other Intervention Name(s)

candesartan

Intervention Description

maximum vasodilation

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Tolerance of the medication.

Time Frame

one year

Secondary Outcome Measure Information:

Title

Decrease of severity of mitral regurgitation.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maurice E. Sarano, M.D.

Organizational Affiliation

Mayo Clinic Foundation

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905'

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Angiotensin-II Blockade in Mitral Regurgitation

We'll reach out to this number within 24 hrs