Trial Outcomes & Findings for Aortic Stenosis and PhosphodiEsterase Type 5 iNhibition (ASPEN): A Pilot Study (NCT NCT01275339)
NCT ID: NCT01275339
Last Updated: 2019-04-17
Results Overview
Measurement of e' (average of septal and lateral) on echo at each of the time points specified.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
10 participants
Primary outcome timeframe
Baseline, 12 weeks, and 6 months
Results posted on
2019-04-17
Participant Flow
Participant milestones
| Measure |
Tadalafil in Diabetic Cohort
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
Tadalafil in Non-Diabetic Cohort
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Non-Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
2
|
0
|
4
|
4
|
|
Overall Study
COMPLETED
|
1
|
0
|
3
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Tadalafil in Diabetic Cohort
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
Tadalafil in Non-Diabetic Cohort
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Non-Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
|---|---|---|---|---|
|
Overall Study
Referred for surgery for AS symptoms
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Aortic Stenosis and PhosphodiEsterase Type 5 iNhibition (ASPEN): A Pilot Study
Baseline characteristics by cohort
| Measure |
Tadalafil in Diabetic Cohort
n=2 Participants
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
Tadalafil in Non-Diabetic Cohort
n=4 Participants
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Non-Diabetic Cohort
n=4 Participants
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
—
|
81.25 years
n=5 Participants
|
75.5 years
n=4 Participants
|
75.7 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
—
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, 12 weeks, and 6 monthsPopulation: There were 0 enrolled that were randomized to placebo in the diabetic cohort; the total number enrolled in the study was small, so this happened randomly.
Measurement of e' (average of septal and lateral) on echo at each of the time points specified.
Outcome measures
| Measure |
Tadalafil in Diabetic Cohort
n=2 Participants
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
Tadalafil in Non-Diabetic Cohort
n=4 Participants
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Non-Diabetic Cohort
n=4 Participants
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
|---|---|---|---|---|
|
Diastolic Function as Measured by Tissue Doppler e'
Baseline
|
4.59 cm/sec
Interval 3.52 to 5.65
|
—
|
5.97 cm/sec
Interval 5.0 to 6.52
|
5.28 cm/sec
Interval 4.48 to 6.21
|
|
Diastolic Function as Measured by Tissue Doppler e'
12 weeks
|
3.75 cm/sec
Interval 3.21 to 4.28
|
—
|
6.44 cm/sec
Interval 5.31 to 7.21
|
4.88 cm/sec
Interval 4.36 to 5.61
|
|
Diastolic Function as Measured by Tissue Doppler e'
6 months
|
4.63 cm/sec
Interval 3.91 to 5.34
|
—
|
6.16 cm/sec
Interval 4.77 to 7.03
|
5.33 cm/sec
Interval 3.57 to 6.18
|
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsE/e' and deceleration time
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 and 12 weeks and 6 monthsThe following with be reported - frequency of the following: hypotension (SBP \< 90 mmHg), symptomatic hypotension (symptoms of presyncope or syncope associated with SBP \<90), syncope, hospitalization for a cardiac reason, myocardial infarction, new onset or worsening heart failure, and new sustained arrhythmia requiring intervention
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsStroke volume, EF, LV twist, and stress-corrected midwall shortening by echo and 3D multiparametric strain and EF by MRI
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsRelative wall thickness, LV chamber dimensions, and wall thickness
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsLV stiffness, viscoelasticity, and a load independent index of diastolic filling
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 and 12 weeks and 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 and 12 weeks and 6 monthsBNP and systemic markers of collagen turnover and oxidative stress
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 and 12 weeks and 6 monthsAssessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 and 12 weeks and 6 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsTAPSE, s' tissue Doppler, and Tei index
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeks and 6 monthsAortic valve area, transvalvular pressure gradients
Outcome measures
Outcome data not reported
Adverse Events
Tadalafil in Diabetic Cohort
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo in Diabetic Cohort
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Tadalafil in Non-Diabetic Cohort
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo in Non-Diabetic Cohort
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tadalafil in Diabetic Cohort
n=2 participants at risk
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Diabetic Cohort
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
Tadalafil in Non-Diabetic Cohort
n=4 participants at risk
Tadalafil: 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 study completion (6 months). 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.
|
Placebo in Non-Diabetic Cohort
n=4 participants at risk
Placebo: 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 study completion (6 months). 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 is not tolerated, then the dose will be decreased back to 1 pill daily.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
shortness of breath
|
50.0%
1/2 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
25.0%
1/4 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
|
Respiratory, thoracic and mediastinal disorders
orthopnea
|
50.0%
1/2 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
|
Cardiac disorders
lightheadedness
|
50.0%
1/2 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
|
Musculoskeletal and connective tissue disorders
fall
|
0.00%
0/2 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
25.0%
1/4 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
|
Vascular disorders
dilated aorta
|
0.00%
0/2 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
25.0%
1/4 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
|
Musculoskeletal and connective tissue disorders
unsteady
|
0.00%
0/2 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
25.0%
1/4 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
|
Gastrointestinal disorders
nausea
|
0.00%
0/2 • 6 months
In that arm of the study, no patients were enrolled.
|
—
0/0 • 6 months
In that arm of the study, no patients were enrolled.
|
25.0%
1/4 • Number of events 1 • 6 months
In that arm of the study, no patients were enrolled.
|
0.00%
0/4 • 6 months
In that arm of the study, no patients were enrolled.
|
Additional Information
Brian R. Lindman, MD
Washington University School of Medicine
Phone: 615-936-5949
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place