Effect of Angiotensin II Receptor Blockers (ARB) on Left Ventricular Reverse Remodelling After Aortic Valve Replacement in Severe Valvular Aortic Stenosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Odense University Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Odense University Hospital
ClinicalTrials.gov Identifier:
NCT00294775
First received: February 21, 2006
Last updated: June 26, 2009
Last verified: June 2009
  Purpose

The consequence of aortic valve stenosis (AVS) is increased pressure load on the left ventricle which causes left ventricular (LV) hypertrophy, and myocardial stretch will cause activation of cardiac peptides and activation of the renin angiotensin aldosterone system (RAAS). The consequence of LV hypertrophy is increased chamber-stiffness and delayed active LV relaxation which initially will cause diastolic and later systolic dysfunction. In heart failure (HF) and ischemic heart disease the degree of diastolic dysfunction has been demonstrated to correlate with functional class, neurohormonal activation and prognosis which also recently have been suggested for AVS.

With longstanding elevated filling pressures the left atrium (LA) will dilate. Only limited data are available on the degree and importance of LA dilatation in AVS.

When apparent, symptoms of HF in AVS are associated with high mortality rates. If LV systolic dysfunction also is present prognosis will deteriorate further. In these cases aorta valve replacement (AVR) is recommended. AVR will normalize pressure overload and thereby decreases LV hypertrophy. Previously it was believed that in time LV hypertrophy regressed towards normal and even normalized. Recent studies however have demonstrated that LV hypertrophy regression mainly happens during the first year after AVR, and little subsequent changes are seen during the remaining 10 years. Furthermore, patients that experience most regression of hypertrophy have more favourable outcome and better functional class than patients with less regression of hypertrophy. Thus absence of reverse remodelling is associated with poor outcome after AVR. Importantly the regression of LV hypertrophy is closely paralleled by decreasing RAAS hyperactivity.

RAAS hyperactivity may be attenuated pharmacologically with angiotensin II receptor blockers (ARB) which in systemic hypertension with LV hypertrophy has been associated with reverse remodelling.

The hypothesis is that in patients undergoing AVR for symptomatic AVS, 12 months post operative blockade of the angiotensin II receptor will accelerate LV and LA reverse remodelling, reduce filling pressures and suppress neurohormonal activation compared with conventional therapy. This will lead to improved exercise tolerance and due to improved left atrial function reducing the risk of atrial arrythmias.


Condition Intervention Phase
Aortic Valve Stenosis
Left Ventricular Hypertrophy
Atrial Fibrillation
Drug: Candesartan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Left Ventricular Reverse Remodelling After Aortic Valve Replacement in Severe Valvular Aortic Stenosis - Effect of Blockade of the Angiotensin-II Receptor

Resource links provided by NLM:


Further study details as provided by Odense University Hospital:

Primary Outcome Measures:
  • LV mass index
  • LA volume index
  • Plasma nt-pro BNP concentration

Secondary Outcome Measures:
  • Diastolic E/e' ratio
  • Overall LV function assessed by the Doppler echocardiographic Tei Index
  • Regional LV function assessed with tissue Doppler imaging
  • LV end systolic and end diastolic volume index
  • Atrial arrhythmias assessed with 48h Holter after 12 months
  • Exercise capacity after 12 months
  • Serial changes in LV diastolic, overall LV function and regional LV systolic function
  • Assess serial changes in plasma nt-pro BNP, ANP, and renin

Estimated Enrollment: 140
Study Start Date: February 2006
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Symptomatic severe AVS referred for valve replacement (mechanic prosthesis or bioprosthesis) at Odense University Hospital
  2. Signed informed consent

Exclusion Criteria:

  1. Severe renal failure (s-creatinine >300 mmole/l)
  2. Moderate or severe hepatic failure
  3. Moderate or severe LV systolic dysfunction (LVEF<40%)
  4. Patients already treated with ACE-I or ARB
  5. Known intolerance for ARB
  6. Unwilling to participate in the study
  7. Poor echocardiographic window
  8. Pregnant women
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00294775

Locations
Denmark
Cardiology Department, Odense University hospital
Odense, Fyn, Denmark, 5000
Sponsors and Collaborators
Odense University Hospital
Investigators
Study Director: Torben Haghfelt, Md, DMSc Kardiologisk forskningsenhed, OUH
Principal Investigator: Jordi S Dahl, MD, MMSci Kardiologisk forskningsenhed, OUH
Study Chair: Henrik Nissen, MD, PhD Kardiologisk forskningsenhed, OUH
Study Chair: Jacob E Moller, Md, Ph.D Kardiologisk forskningsenhed, OUH
Study Chair: Lars Videbæk, MD, Ph.d Kardiologisk forskningsenhed, OUH
Study Chair: Lars I Andersen, MD, DMSc Department of thoracic surgery, OUH
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00294775     History of Changes
Other Study ID Numbers: EudraCT number 2005-001930-34
Study First Received: February 21, 2006
Last Updated: June 26, 2009
Health Authority: Denmark: Danish Medicines Agency
Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency

Keywords provided by Odense University Hospital:
diastolic dysfunction
Reverse Remodelling

Additional relevant MeSH terms:
Aortic Valve Stenosis
Atrial Fibrillation
Constriction, Pathologic
Hypertrophy
Hypertrophy, Left Ventricular
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Pathological Conditions, Anatomical
Heart Valve Diseases
Ventricular Outflow Obstruction
Cardiomegaly
Angiotensin II
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014