Aortic Valve StenosisPhase 3ROCK-ASNCT00699452
The Potential of Candesartan to Retard the Progression of Aortic Stenosis
A Phase 3 study testing candesartan in people with Aortic Valve Stenosis, run by University of Helsinki at 1 site in Finland.
Trial summary
The present study defines a blinded, randomized, placebo-controlled, prospective study, the aim of which is to determine the influence of effective treatment with Type 1 angiotensin II (Ang II) receptor (AT-1R) antagonist, using candesartan (target dose 16 mg) on stenotic aortic valves. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Stenosis
- What is being tested?
- candesartan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteFinland
- Study dates
- May 2009to Dec 2014
- Phase
- Phase 3
- 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
- 120 consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery.
Who cannot join
- Individuals with past myocardial infarction, more than mild mitral valve disease, or previous cardiac surgery will be excluded.
- Patients with heart failure who need urgent surgery or those with hypotension (systolic blood pressure below 110 mm Hg) will be excluded.
- Patients already taking ACE inhibitors or AT-1R antagonists will be excluded from the study population.
- Other exclusion criteria include the following:
- Complicated diabetes
- Primary cardiomyopathy
Show all 13Show fewer
- Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have a positive serum pregnancy test
- History of malignancy (unless a documented disease free period exceeding 5-years is present) with the exception of basal cell or squamous cell carcinoma of the skin. Women with a history of cervical dysplasia would be permitted to enter the study provided they had 3 consecutive clear Papanicolaou (Pap) smears
- Hypothyroidism (TSH 1.5xULN)
- History of alcohol or drug abuse within the last 5 years (this may affect compliance)
- Unexplained creatine kinase (CK 3xULN) (To protect patient safety)
- Serum creatinine >176 umol/L (2.0mg/dL)
- Participation in another investigational drug study less than 4 weeks before enrolment in the study, or according to subjects local ethics committee requirements where a larger period is stipulated (to avoid potential misinterpretation of overlapping adverse events)
Trial locations and contacts
1 site in 1 country.
Finland1 site, 1 recruiting
- Recruiting
Division of Cardiology, Helsinki University Central Hospital
Helsinki, 00029
Markku Kupari, MD, PhD, 358-9-4717-2441, markku.kupari@hus.fi
Satu Helske, MD, PhD, 358-9-681-411, satu.helske@wri.fi
About this study
Official title: The Potential of Candesartan to Retard the Progression of Aortic Stenosis Influences of Medical Therapy to the Atheroinflammatory Process in Stenotic Aortic Valves
The present study defines a blinded, randomized, placebo-controlled, prospective study, the aim of which is to determine the influence of effective treatment with Type 1 angiotensin II (Ang II) receptor (AT-1R) antagonist, using candesartan (target dose 16 mg) on stenotic aortic valves. The investigators will specifically quantify whether candesartan attenuates the key pathogenic mechanisms of aortic valve stenosis, namely inflammation, fibrosis, elastin degradation, calcification, and neovascularization.
Read the detailed description
We will include in the study 120 consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery. Patients who can be put on the hospital's normal waiting list for elective angiography (i.e who do not need urgent surgery) and who give their informed consent, will be randomized into two groups to start therapy with candesartan (8 mg/d for 2 weeks, and then 16 mg/d until surgery) or placebo. On average, the overall duration of the drug intervention will be 3 months, i.e., the average time in our institution from referral to surgery. In addition, patients (n=50) undergoing aortic valve replacement surgery due to aortic regurgitation caused by dilation of the aortic root will be included. This population consists of both patients with early sclerotic, i.e., pre-stenotic, changes in their aortic valves (n=30) and of patients without any sclerotic or stenotic changes in their aortic valves (n=20). The group with sclerotic changes in their aortic valves (n=30) will be divided into two groups to receive candesartan (8 mg/d 2 wk, and then 16 mg/d until surgery) (n=15) or placebo (n=15). The removed aortic valves will be examined utilizing real-time PCR, autoradiography, fluorometry, immunohistochemistry, double immunofluorescence, confocal microscopy, and enzyme immunoassays. With these techniques, several markers of inflammation, calcification, fibrosis, and the amount of lipid accumulation and oxidation of LDL in the valves will be examined.
- Conditions
- Aortic Valve Stenosis
- Being tested
- candesartan, placebo
- Keywords
- aortic stenosis, valve, candesartan
- 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.
candesartanDrug
Also called Atacand
Candesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months)
placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Candesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months) Receives: Drug: candesartan |
| 2 | Placebo comparator | Placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The degree of inflammation in stenotic aortic valves
Measured: 3-5 months
Secondary outcomes (1)
The degree of calcification, lipid accumulation, and fibrosis in stenotic aortic valves
Measured: 3-5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2008 (estimated)
- Study startMay 2009
- Primary completionDec 2012 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve StenosisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Investigators
- Markku Kupari, MD, PhD, Principal investigator, Division of Cardiology, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00699452
- Sponsor's protocol ID
- ROCK-AS
- Acronym
- ROCK-AS
- Status last verified
- May 2009
- First submitted
- 16 Jun 2008
- Last updated
- 19 May 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Helske-Suihko S, Laine M, Lommi J, Kaartinen M, Werkkala K, Kovanen PT, Kupari M. Is blockade of the Renin-Angiotensin system able to reverse the structural and functional remodeling of the left ventricle in severe aortic stenosis? J Cardiovasc Pharmacol. 2015 Mar;65(3):233-40. doi: 10.1097/FJC.0000000000000182.
PubMed 25469804
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Potential of Candesartan to Retard the Progression of Aortic Stenosis Influences of Medical Therapy to the Atheroinflammatory Process in Stenotic Aortic Valves
- ClinicalTrials.gov ID
- NCT00699452
- Acronym / sponsor ID
- ROCK-AS / ROCK-AS
- Conditions
- Aortic Valve Stenosis
- Keywords
- aortic stenosis, valve, candesartan
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- May 2009
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 18 Jun 2008 (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.
The present study defines a blinded, randomized, placebo-controlled, prospective study, the aim of which is to determine the influence of effective treatment with Type 1 angiotensin II (Ang II) receptor (AT-1R) antagonist, using candesartan (target dose 16 mg) on stenotic aortic valves. The investigators will specifically quantify whether candesartan attenuates the key pathogenic mechanisms of aortic valve stenosis, namely inflammation, fibrosis, elastin degradation, calcification, and neovascularization.
Detailed description
We will include in the study 120 consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery. Patients who can be put on the hospital's normal waiting list for elective angiography (i.e who do not need urgent surgery) and who give their informed consent, will be randomized into two groups to start therapy with candesartan (8 mg/d for 2 weeks, and then 16 mg/d until surgery) or placebo. On average, the overall duration of the drug intervention will be 3 months, i.e., the average time in our institution from referral to surgery. In addition, patients (n=50) undergoing aortic valve replacement surgery due to aortic regurgitation caused by dilation of the aortic root will be included. This population consists of both patients with early sclerotic, i.e., pre-stenotic, changes in their aortic valves (n=30) and of patients without any sclerotic or stenotic changes in their aortic valves (n=20). The group with sclerotic changes in their aortic valves (n=30) will be divided into two groups to receive candesartan (8 mg/d 2 wk, and then 16 mg/d until surgery) (n=15) or placebo (n=15). The removed aortic valves will be examined utilizing real-time PCR, autoradiography, fluorometry, immunohistochemistry, double immunofluorescence, confocal microscopy, and enzyme immunoassays. With these techniques, several markers of inflammation, calcification, fibrosis, and the amount of lipid accumulation and oxidation of LDL in the valves will be examined.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: candesartanCandesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months) |
| 2 | Placebo comparator | Drug: placeboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 120 consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery.
Key exclusion criteria (13 listed)
- Individuals with past myocardial infarction, more than mild mitral valve disease, or previous cardiac surgery will be excluded.
- Patients with heart failure who need urgent surgery or those with hypotension (systolic blood pressure below 110 mm Hg) will be excluded.
- Patients already taking ACE inhibitors or AT-1R antagonists will be excluded from the study population.
- Other exclusion criteria include the following:
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 |
|---|---|---|
| candesartanAlso: AtacandCandesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months) | Drug | 1 |
| placeboplacebo | Drug | 2 |
Primary outcome
The degree of inflammation in stenotic aortic valves
Time frame: 3-5 months
1 secondary outcome
The degree of calcification, lipid accumulation, and fibrosis in stenotic aortic valves
Time frame: 3-5 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2009.
- Derived from this study: PubMed 25469804Helske-Suihko S, Laine M, Lommi J, Kaartinen M, Werkkala K, Kovanen PT, Kupari M. Is blockade of the Renin-Angiotensin system able to reverse the structural and functional remodeling of the left ventricle in severe aortic stenosis? J Cardiovasc Pharmacol. 2015 Mar;65(3):233-40. doi: 10.1097/FJC.0000000000000182.
Related trials for Aortic Valve Stenosis
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Active, not recruitingObservational study
Intravascular Lithotripsy in High Risk Calcified Iliac Anatomy for Transfemoral TAVR
Iliac Disease, Aortic Valve Stenosis
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Recruiting
Exercise and Diet Supplements for Older Patients Undergoing TAVI: the IRON-TAVI Trial
Aortic Stenosis Disease, Aortic Stenosis Symptomatic
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.
Markku Kupari, MD, PhD principal investigator
Division of Cardiology, Helsinki University Central Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing candesartan in people with Aortic Valve Stenosis, run by University of Helsinki at 1 site in Finland.
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 1 inclusion and 13 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 19 May 2009. 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 Finland. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Markku Kupari, MD, PhD (358-9-4717-2441, markku.kupari@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The degree of inflammation in stenotic aortic valves (time frame: 3-5 months). 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 NCT00699452, which also lists 1 linked publication.
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 19 May 2009.