Aortic Stenosis and PhosphodiEsterase Type 5 iNhibition (ASPEN): A Pilot Study

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2013
• Main ID: NCT01275339
• Date of registration: 06/01/2011
• Primary sponsor: Washington University School of Medicine
• Public title: Aortic Stenosis and PhosphodiEsterase Type 5 iNhibition (ASPEN): A Pilot Study ASPEN
• Scientific title: Aortic Stenosis and PhosphodiEsterase Type 5 iNhibition (ASPEN): A Pilot Study
• Date of first enrolment: December 2012
• Target sample size: 56
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01275339
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Brian R. Lindman, MD

• Name: Brian R. Lindman, MD

• Name: Brian R. Lindman, MD, MSCI
• Affiliation: Washington University School of Medicine

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with moderate to severe aortic stenosis (AVA < 1.5 cm2)

- Left ventricular hypertrophy

- Diastolic dysfunction as evidenced by tissue Doppler e' (average of septal and
lateral) = 7 cm/s

- EF = 50%

- None or minimal symptoms related to aortic stenosis (NYHA = 2)

- The subject and treating physician are not planning on a valve replacement procedure
to occur during the next 6 months

- Ambulatory

- Normal sinus rhythm

- 18 years of age and older

- Able and willing to comply with all the requirements for the study

Exclusion Criteria:

- Need for ongoing nitrate medications

- SBP < 110mmHg or MAP < 75mmHg

- Moderately severe or severe mitral regurgitation

- Moderately severe or severe aortic regurgitation

- Contraindication to MRI

- Creatinine clearance < 30 mL/min

- Cirrhosis

- Pulmonary fibrosis

- Increased risk of priapism

- 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)

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Aortic Stenosis

LV Remodeling, Hypertrophy

Intervention(s)

Drug: Placebo

Drug: Tadalafil

Primary Outcome(s)

Change in diastolic function as measured by tissue Doppler e' [Time Frame: 12 weeks and 6 months (primary)]

Change in LV longitudinal peak systolic strain by echo [Time Frame: 12 weeks and 6 months (primary)]

Change in LV mass on MRI [Time Frame: 6 months]

Secondary Outcome(s)

Change in 6 minute walk distance [Time Frame: 6 and 12 weeks and 6 months]

Change in AS severity [Time Frame: 12 weeks and 6 months]

Change in circulating neurohormonal markers [Time Frame: 6 and 12 weeks and 6 months]

Change in indices of systolic function [Time Frame: 12 weeks and 6 months]

Change in LV hypertrophic remodeling [Time Frame: 12 weeks and 6 months]

Change in myocardial fibrosis (ECV) on MRI [Time Frame: 6 months]

Change in novel echocardiographic indices of diastolic function [Time Frame: 12 weeks and 6 months]

Change in other echocardiographic indices of diastolic function [Time Frame: 12 weeks and 6 months]

Change in pulmonary artery pressure and pulmonary vascular resistance as assessed by echo [Time Frame: 12 weeks and 6 months]

Change in quality of life [Time Frame: 6 and 12 weeks and 6 months]

Change in RV function [Time Frame: 12 weeks and 6 months]

Change in systemic blood pressure [Time Frame: 6 and 12 weeks and 6 months]

Safety and tolerability [Time Frame: 6 and 12 weeks and 6 months]

Secondary ID(s)

10-1334b

Source(s) of Monetary Support

Please refer to primary and secondary sponsors