Aortic StenosisPhase 4ASPEN-AVRNCT01272388
Aortic Stenosis and PhosphodiEsterase iNhibition With Aortic Valve Replacement (ASPEN-AVR): A Pilot Study
A Phase 4 study testing Tadalafil in people with Aortic Stenosis, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Currently, aortic stenosis (AS) is considered a "surgical disease" with no medical therapy available to improve any clinical outcomes, including symptoms, time to surgery, or long-term survival. Thus far, randomized studies involving statins have not been promising with respect to slowing progressive valve stenosis. 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?
- Tadalafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Apr 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with severe aortic stenosis (AVA < 1.0 cm2)
- Left ventricular hypertrophy
- EF ≥ 45%
- NYHA functional class ≥ 2
- Ambulatory (able to perform a 6 minute walk test)
- Normal sinus rhythm
- 18 years of age and older
- Able and willing to comply with all the requirements for the study
Who cannot join
- Need for ongoing nitrate medications
- SBP < 110mmHg or MAP < 75mmHg
- Moderately severe or severe mitral regurgitation
- Moderately severe or severe aortic regurgitation
- Creatinine clearance < 30 mL/min
- Increased risk of priapism
Show all 16Show fewer
- Retinal or optic nerve problems or unexplained visual disturbance
- If a subject requires ongoing use of an alpha antagonist typically used for benign prostatic hyperplasia (BPH) (prazosin, terazosin, doxazosin, or tamsulosin), SBP < 120 mmHg or MAP < 80 mmHg is excluded
- Need for ongoing use of a potent CYP3A inhibitor or inducer (ritonavir, ketoconazole, itraconazole, rifampin)
- Cirrhosis
- Pulmonary fibrosis
- Current or recent (≤ 30 days) acute coronary syndrome
- O2 sat < 90% on room air
- Females that are pregnant or believe they may be pregnant
- Any condition which the PI determines will place the subject at increased risk or is likely to yield unreliable data
- Unwilling to provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Currently, aortic stenosis (AS) is considered a "surgical disease" with no medical therapy available to improve any clinical outcomes, including symptoms, time to surgery, or long-term survival. Thus far, randomized studies involving statins have not been promising with respect to slowing progressive valve stenosis. Beyond the valve, two common consequences of aortic stenosis are hypertrophic remodeling of the left ventricle (LV) and pulmonary venous hypertension; each of these has been associated with worse heart failure symptoms, increased operative mortality, and worse long-term outcomes. Whether altering LV structural abnormalities, improving LV function, and/or reducing pulmonary artery pressures with medical therapy would improve clinical outcomes in patients with AS has not been tested. Animal models of pressure overload have demonstrated that PDE5 inhibition influences NO-cGMP signaling in the LV and favorably impacts LV structure and function, but this has not been tested in humans with AS. Studies in humans with left-sided heart failure and pulmonary venous hypertension have shown that PDE5 inhibition improves functional capacity and quality of life, but patients with AS were not included in those studies. The investigators hypothesize that PDE5 inhibition with tadalafil will upregulate NO-cGMP signaling, reduce oxidative stress, and have a favorable impact on LV structure and function as well as pulmonary artery pressures and quality of life. In this pilot study, the investigators anticipate that short-term administration of tadalafil to patients with AS will be safe and well-tolerated.
Read the detailed description
Patients with severe symptomatic AS who will undergo elective aortic valve replacement will be eligible for this randomized, double-blind, placebo-controlled, pilot study. Prior to randomization, subjects will have testing including: 6 minute walk, quality of life questionnaire, blood draw, and an echocardiogram. If an initial monitored dose of tadalafil is tolerated, participants will be randomized 2:1 to tadalafil vs. placebo. After 4 weeks on drug or placebo, subjects will have the same baseline testing repeated. At the time of aortic valve replacement surgery, the aortic valve and a small piece of LV myocardium will be taken for several analyses.
- Conditions
- Aortic Stenosis
- Being tested
- Tadalafil, Placebo
- Keywords
- Aortic valve stenosis, Tadalafil, Phosphodiesterase inhibitors, Hypertension, pulmonary, Hypertrophy, left ventricular
- Medical subject headings
- Aortic Valve Stenosis, Hypertension, Pulmonary, Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Cialis, Adcirca
Active drug will be encapsulated to look identical to the placebo pill. Subjects will take a single oral dose of tadalafil once daily from the time of randomization until the surgical date (~4 weeks). Subjects will begin by taking 20 mg (1 pill) daily for 3 days before having the dose increased to 40 mg (2 pills) once daily. If the increase to 40mg daily is not tolerated, then the dose will be decreased back to 20mg daily.
PlaceboDrug
The placebo pill will be encapsulated to look identical to the active drug pill. Subjects will take a single oral dose of placebo once daily from the time of randomization until the surgical date (~4 weeks). Subjects will begin by taking 1 pill daily for 3 days before having the dose increased to 2 pills once daily. If the increase to 2 pills daily is not tolerated, then the dose will be decreased back to 1 pill daily.
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil | Active comparator | Not described Receives: Drug: Tadalafil |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quality of Life as Assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
KCCQ overall summary score is reported. Scale is 0-100 (higher value is better).
Measured: Baseline and 4 weeks
Secondary outcomes (1)
6 Minute Walk Distance
How far the subject walked in 6 minutes.
Measured: Baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionApr 2011
- Study completionApr 2012
Why it stopped: We designed a different pilot trial based on data obtained after this study started - the 2 studies were too overlapping to continue both.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Lindman, MD, Washington University School of Medicine
- Investigators
- Brian R. Lindman, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01272388
- Sponsor's protocol ID
- 10-1334a
- Acronym
- ASPEN-AVR
- Status last verified
- Sep 2018
- First submitted
- 6 Jan 2011
- Last updated
- 12 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aortic Stenosis and PhosphodiEsterase iNhibition With Aortic Valve Replacement (ASPEN-AVR): A Pilot Study
- ClinicalTrials.gov ID
- NCT01272388
- Acronym / sponsor ID
- ASPEN-AVR / 10-1334a
- Conditions
- Aortic Stenosis
- Keywords
- Aortic valve stenosis, Tadalafil, Phosphodiesterase inhibitors, Hypertension, pulmonary, Hypertrophy, left ventricular
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: We designed a different pilot trial based on data obtained after this study started - the 2 studies were too overlapping to continue both.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 7 Jan 2011 (estimated)
- Results
- Posted 12 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Currently, aortic stenosis (AS) is considered a "surgical disease" with no medical therapy available to improve any clinical outcomes, including symptoms, time to surgery, or long-term survival. Thus far, randomized studies involving statins have not been promising with respect to slowing progressive valve stenosis. Beyond the valve, two common consequences of aortic stenosis are hypertrophic remodeling of the left ventricle (LV) and pulmonary venous hypertension; each of these has been associated with worse heart failure symptoms, increased operative mortality, and worse long-term outcomes. Whether altering LV structural abnormalities, improving LV function, and/or reducing pulmonary artery pressures with medical therapy would improve clinical outcomes in patients with AS has not been tested. Animal models of pressure overload have demonstrated that PDE5 inhibition influences NO-cGMP signaling in the LV and favorably impacts LV structure and function, but this has not been tested in humans with AS. Studies in humans with left-sided heart failure and pulmonary venous hypertension have shown that PDE5 inhibition improves functional capacity and quality of life, but patients with AS were not included in those studies. The investigators hypothesize that PDE5 inhibition with tadalafil will upregulate NO-cGMP signaling, reduce oxidative stress, and have a favorable impact on LV structure and function as well as pulmonary artery pressures and quality of life. In this pilot study, the investigators anticipate that short-term administration of tadalafil to patients with AS will be safe and well-tolerated.
Detailed description
Patients with severe symptomatic AS who will undergo elective aortic valve replacement will be eligible for this randomized, double-blind, placebo-controlled, pilot study. Prior to randomization, subjects will have testing including: 6 minute walk, quality of life questionnaire, blood draw, and an echocardiogram. If an initial monitored dose of tadalafil is tolerated, participants will be randomized 2:1 to tadalafil vs. placebo. After 4 weeks on drug or placebo, subjects will have the same baseline testing repeated. At the time of aortic valve replacement surgery, the aortic valve and a small piece of LV myocardium will be taken for several analyses.
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 |
|---|---|---|
| Tadalafil | Active comparator | Drug: Tadalafil |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with severe aortic stenosis (AVA < 1.0 cm2)
- Left ventricular hypertrophy
- EF ≥ 45%
- NYHA functional class ≥ 2
- Ambulatory (able to perform a 6 minute walk test)
Key exclusion criteria (16 listed)
- Need for ongoing nitrate medications
- SBP < 110mmHg or MAP < 75mmHg
- Moderately severe or severe mitral regurgitation
- Moderately severe or severe aortic regurgitation
- Creatinine clearance < 30 mL/min
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 |
|---|---|---|
| TadalafilAlso: Cialis, AdcircaActive drug will be encapsulated to look identical to the placebo pill. Subjects will take a single oral dose of tadalafil once daily from the time of randomization until the surgical date (~4 weeks). Subjects will begin by taking 20 mg (1 pill) daily for 3 days before having the dose increased to 40 mg (2 pills) once daily. If the increase to 40mg daily is not tolerated, then the dose will be decreased back to 20mg daily. | Drug | Tadalafil |
| PlaceboThe placebo pill will be encapsulated to look identical to the active drug pill. Subjects will take a single oral dose of placebo once daily from the time of randomization until the surgical date (~4 weeks). Subjects will begin by taking 1 pill daily for 3 days before having the dose increased to 2 pills once daily. If the increase to 2 pills daily is not tolerated, then the dose will be decreased back to 1 pill daily. | Drug | Placebo |
Primary outcome
Quality of Life as Assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: Baseline and 4 weeks
KCCQ overall summary score is reported. Scale is 0-100 (higher value is better).
1 secondary outcome
6 Minute Walk Distance
Time frame: Baseline and 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Intravascular Lithotripsy in High Risk Calcified Iliac Anatomy for Transfemoral TAVR
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NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
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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.
Brian R. Lindman, MD principal investigator
Washington University School of Medicine
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 Tadalafil in people with Aortic Stenosis, run by Washington University School of Medicine at 1 site in United States.
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 8 inclusion and 16 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: stopped early, as of the sponsor's last update on 12 Sep 2018. 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 United States. 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?
Yes. Results are posted in the registry (first posted 12 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quality of Life as Assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (time frame: Baseline and 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Sep 2018.