Aortic StenosisPhase 4NCT00252317
Acute Haemodynamic Effects of Treatment With Angiotensin Converting Enzyme (ACE)-Inhibitors in Patients With Symptomatic Aortic Stenosis
A Phase 4 study testing Captopril and Trandolapril and Captopril Test Dose and Trandolapril in people with Aortic Stenosis, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis
- What is being tested?
- Captopril and Trandolapril and Captopril Test Dose and Trandolapril
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2005to Oct 2008
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Dizziness at exertion
- Previous pulmonary oedema
- Patients in New York Heart Association functional class II-IV
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet, Copenhagen University Hospital
Copenhagen, KBH Ø, 2100
Morten Dalsgaard, MD, +45 35 45 06 29, md@dadlnet.dk
About this study
Official title: Acute Haemodynamic Effects of Treatment With ACE-Inhibitors in Patients With Symptomatic Aortic Stenosis (ACCESS)
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.
Read the 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.
- Conditions
- Aortic Stenosis
- Being tested
- Captopril and Trandolapril, Captopril Test Dose and Trandolapril
- Keywords
- Aortic stenosis, ACE-inhibitores
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Captopril and TrandolaprilDrug
Caps Captopril 6.25 mg test dose and Caps Trandolapril 0.5mg or 1.0mg or 2.0 mg (depending on symptoms ie. hypotension)
Captopril Test Dose and TrandolaprilDrug
Caps Captopril 6.25 mg test dose and Caps Trandolapril 0.5mg or 1.0mg or 2.0 mg (depending on symptoms ie. hypotension)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Captopril test dose and Trandolapril Receives: Drug: Captopril and Trandolapril; Drug: Captopril Test Dose and Trandolapril |
| 2 | Placebo comparator | Not described Receives: Drug: Captopril and Trandolapril; Drug: Captopril Test Dose and Trandolapril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment with ACE-inhibitors improves haemodynamic parameters in patients with severe aortic stenosis.
Measured: 8 weeks
Secondary outcomes (5)
Treatment with ACE-inhibitors:
Measured: 8 weeks
Increases working capacity in patients with severe aorta stenosis.
Measured: 8 weeks
Improves systolic and diastolic function on left ventricle.
Measured: 8 weeks
In patients with severe aortic stenosis is safe.
Measured: 8 weeks
Degrease wall stress in left ventricle.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2005 (estimated)
- Study startNov 2005
- Study completionOct 2008 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Investigators
- Morten Dalsgaard, MD, Principal investigator, Copenhagen University Hospital, RigshospitaletChristian Hassager, MD, Phd, Principal investigator, Copenhagen University Hospital, RigshospitaletPeter Clemmensen, MD, Phd, Principal investigator, Copenhagen University Hospital, RigshospitaletPeer Grande, MD, Phd, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00252317
- Sponsor's protocol ID
- 3d
- Status last verified
- Nov 2007
- First submitted
- 10 Nov 2005
- Last updated
- 3 Sep 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Routledge HC, Townend JN. ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity? J Hum Hypertens. 2001 Oct;15(10):659-67. doi: 10.1038/sj.jhh.1001260.
PubMed 11607794Dalsgaard M, Kjaergaard J, Pecini R, Iversen KK, Kober L, Moller JE, Grande P, Clemmensen P, Hassager C. Predictors of exercise capacity and symptoms in severe aortic stenosis. Eur J Echocardiogr. 2010 Jul;11(6):482-7. doi: 10.1093/ejechocard/jeq002. Epub 2010 Feb 6.
PubMed 20139439