Acute Haemodynamic Effects of Treatment With Angiotensin Converting Enzyme (ACE)-Inhibitors in Patients With Symptomatic Aortic Stenosis
Information source: Rigshospitalet, Denmark
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Aortic Stenosis
Intervention: Captopril and Trandolapril (Drug); Captopril Test Dose and Trandolapril (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Rigshospitalet, Denmark Official(s) and/or principal investigator(s):
Morten Dalsgaard, MD, Principal Investigator, Affiliation: Rigshospitalet, Denmark
Christian Hassager, MD, Phd, Principal Investigator, Affiliation: Rigshospitalet, Denmark
Peter Clemmensen, MD, Phd, Principal Investigator, Affiliation: Rigshospitalet, Denmark
Peer Grande, MD, Phd, Principal Investigator, Affiliation: Rigshospitalet, Denmark
Summary
Abundant evidence suggests that Angiotensin Converting Enzyme (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.
Clinical Details
Official title: Acute Haemodynamic Effects of Treatment With ACE-Inhibitors in Patients With Symptomatic Aortic Stenosis (ACCESS)
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Treatment with ACE-inhibitors improves haemodynamic parameters in patients with severe aortic stenosis.
Secondary outcome: 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.
Detailed description:
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 angiotensin 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 of 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
- B-type natriuretic peptide (BNP)
Patients
32 patients with symptomatic aorta stenosis recruited from Rigshospitalet 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-test dose 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 in 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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:
- 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
Locations and Contacts
Rigshospitalet, Copenhagen University Hospital, Copenhagen, KBH Ø 2100, Denmark; Recruiting
Morten Dalsgaard, MD, Phone: +45 35 45 06 29, Email: md@dadlnet.dk
Additional Information
Related publications: Routledge HC, Townend JN. ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity? J Hum Hypertens. 2001 Oct;15(10):659-67. Review.
Starting date: November 2005
Ending date: October 2008
Last updated: September 2, 2008
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