Aboundant evidence suggests that ACE inhibition potentially could reduce the hazardous effects of aortic stenosis and improve haemodynamics. The treatment seems safe even in patients with severe stenosis. There are however no randomised clinical trials that can confirm this hypothesis.

Condition	Intervention	Phase
Aortic Stenosis	Drug: Captopril and Trandolapril	Phase IV

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcomes: Treatment with ACE-inhibitors improves haemodynamic parameters in patients with severe aortic stenosis.
Secondary Outcomes: Treatment with ACE-inhibitors:; -Increases working capacity in patients with severe aorta stenosis.; -Improves systolic and diastolic function on left ventricle.; -In patients with severe aortic stenosis is safe.; -Degrease wall stress in left ventricle.
Expected Total Enrollment:  64

Traditionally vasodilators are contraindicated in patients with aortic stenosis. Although no controlled data exists it is believed to be hazardous to reduce afterload, including treatment with Angiotensine converting enzyme (ACE) inhibitors, in these patients with aortic stenosis due to the risk of increased transaortic gradient and thus severe hypotension and myocardial hypoperfusion. There is now growing evidence both experimental and clinical that ACE inhibition could have beneficial effects on left ventricular hypertrophy, diastolic function, acute, and possibly chronic haemodynamic parameters in patients with aortic stenosis.

There is, however, a lack a clinical randomized trials that could confirm these findings.

Aims Prospective double blinded randomised study investigating the safety and effects of treatment with ACE-inhibitor in patients with severe aortic stenosis. Effects will be measured on

• Invasive measured haemodynamic parameters (Swann-Ganz)
• Working capacity
• Diastolic and systolic function (measured with tissue Doppler echocardiography)
• Blood pressure
• BNP

Patients 32 patients with symptomatic aorta stenosis recruited from Rigshospitalets department of cardiology. Patients referred for evaluation prior to surgical intervention with insertion of a valvular prosthesis will be screened.

Additional 32 patients with asymptomatic aorta stenosis will be recruited from Rigshospitalet and other cardiology departments.

Methods

Recruitment Patients with symptomatic severe aortic stenosis scheduled for aortic valve replacement at The Heart Centre at Rigshospitalets department of cardiology will be recruited.

Patients with severe asymptomatic aortic stenosis on Rigshospitalet will be recruited. If it is necessary patients from other hospitals will be recruited.

Randomisation After baseline screening patients will be randomized to active treatment or placebo. Half of the patients will have ACE-inhibitors (Captopril-testdose after this Trandolapril)the other half placebo.

Administration of medicine ACE-inhibitor/placebo administration will be double blinded and performed by a hospital pharmacist not involved in any other part of the project.

All patients will be hospitalised at the intensive care unit for the first 3 days to evaluate the acute haemodynamic changes when they start the treatment. If the patients have no symptoms after the 3 days they will discharge for further treatment for up to 8 weeks. Visits are planned after 2 and 8 weeks.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Inclusion criteria’s

  • Valvular aortic stenosis with a aortic valve area <1,0 cm2
  • Age > 18 years
  • Willingness to give written informed consent
  • For patients with symptomatic aortic stenosis at least one of following
  • Stable angina pectoris
  • Syncope at exertion
  • Dizziness at exertion
  • Previous pulmonary oedema
  • Patients in New York Heart Association functional class II-IV

Exclusion Criteria:

• Exclusion criteria’s

  • Sitting systolic pressure < 100 mmHg
  • Creatinine > 200 mM at screening
  • Renal artery stenosis
  • Pregnancy or planned pregnancy
  • Participation in other studies
  • Any patient characteristic that may interfere with compliance with the study protocol
  • Treated with ACE-inhibitor or angiotensin receptor blocker within the last month
  • Known allergy to ACE-inhibitors

Please refer to this study by ClinicalTrials.gov identifier  NCT00252317

Denmark, KBH Ø
      Rigshospitalet, Copenhagen University Hospital, Copenhagen,  KBH Ø,  2100,  Denmark

Study chairs or principal investigators

Morten Dalsgaard, MD,  Principal Investigator,  Rigshospitalet, Denmark   
Christian Hassager, MD, Phd,  Principal Investigator,  Rigshospitalet, Denmark   
Peter Clemmensen, MD, Phd,  Principal Investigator,  Rigshospitalet, Denmark   
Peer Grande, MD, Phd,  Principal Investigator,  Rigshospitalet, Denmark   

Study ID Numbers:  3d
Last Updated:  December 8, 2005
Record first received:  November 10, 2005
ClinicalTrials.gov Identifier:  NCT00252317
Health Authority: Denmark: Danish Medicines Agency
ClinicalTrials.gov processed this record on 2006-01-10