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
- Are there results?
- None posted in the registry
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
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Haemodynamic Effects of Treatment With ACE-Inhibitors in Patients With Symptomatic Aortic Stenosis (ACCESS)
- ClinicalTrials.gov ID
- NCT00252317
- Acronym / sponsor ID
- 3d
- Conditions
- Aortic Stenosis
- Keywords
- Aortic stenosis, ACE-inhibitores
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Nov 2005
- Study completion
- Oct 2008 (estimated)
- First posted
- 11 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Captopril and Trandolapril, Drug: Captopril Test Dose and TrandolaprilCaptopril test dose and Trandolapril |
| 2 | Placebo comparator | Drug: Captopril and Trandolapril, Drug: Captopril Test Dose and Trandolapril |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (8 listed)
- Sitting systolic pressure < 100 mmHg
- Creatinine > 200 mM at screening
- Renal artery stenosis
- Pregnancy or planned pregnancy
- Participation in other studies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Captopril and TrandolaprilCaps Captopril 6.25 mg test dose and Caps Trandolapril 0.5mg or 1.0mg or 2.0 mg (depending on symptoms ie. hypotension) | Drug | 1, 2 |
| Captopril Test Dose and TrandolaprilCaps Captopril 6.25 mg test dose and Caps Trandolapril 0.5mg or 1.0mg or 2.0 mg (depending on symptoms ie. hypotension) | Drug | 1, 2 |
Primary outcome
Treatment with ACE-inhibitors improves haemodynamic parameters in patients with severe aortic stenosis.
Time frame: 8 weeks
5 secondary outcomes
Treatment with ACE-inhibitors:
Time frame: 8 weeks
Increases working capacity in patients with severe aorta stenosis.
Time frame: 8 weeks
Improves systolic and diastolic function on left ventricle.
Time frame: 8 weeks
In patients with severe aortic stenosis is safe.
Time frame: 8 weeks
Degrease wall stress in left ventricle.
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2008.
- Background: PubMed 11607794Routledge 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.
- Derived from this study: PubMed 20139439Dalsgaard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morten Dalsgaard, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
Christian Hassager, MD, Phd principal investigator
Copenhagen University Hospital, Rigshospitalet
Peter Clemmensen, MD, Phd principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment with ACE-inhibitors improves haemodynamic parameters in patients with severe aortic stenosis. (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00252317, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2008.