Fontan Circulation
Conditions
Keywords
Fontan, sildenafil, exercise capacity, Patients with Fontan Circulation
Brief summary
The study will test the hypothesis that a single dose of sildenafil can increase the exercise capacity of pediatric patients with a Fontan Circulation.
Interventions
DRUGSildenafil
oral suspension, 0.5mg/kg, taken once prior to exercise stress test. Enrolled patients will be randomized to receive Sildenafil first and then crossed over to receive the opposite intervention, placebo.
DRUGPlacebo
Patient will receive a look-alike placebo. Enrolled patients will be randomized to receive Placebo first and then crossed over to receive the opposite intervention, Sildenafil.
DRUGSildenafil 2
oral suspension, 0.5mg/kg, taken once prior to exercise stress test. Enrolled patients will receive Sildenafil, the crossed over intervention from their initial intervention (Placebo).
DRUGPlacebo 2
Patient will receive a look-alike placebo. Enrolled patients will receive Placebo, the crossed over intervention from their initial intervention (Sildenafil).
Sponsors
Children's Miracle Network
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 6-17 years * Male or female * Possess Fontan Circulation
Exclusion criteria
* Severe heart failure (New York Heart Ass. functional class IV) * Evidence of Fontan pathway obstruction * History of exercise-induced severe arrhythmias * Pregnancy (known or suspected) * Orthopedic limitations that prevent ambulation on a treadmill * Use of nitroglycerin * Herbal medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Exercise Capacity Measured Via Maximum Oxygen Consumed During Exercise (VO2) | baseline to 1 hour | A change in exercise capacity measured via maximum oxygen consumed during exercise (VO2). The measurement will be obtained from the Exercise Stress Test |
| The Change in Exercise Capacity Measured Via Exercise Time | baseline to 1 hour | A change in exercise capacity measured via exercise time (in minutes). The measurement will be obtained from the Exercise Stress Test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Exercise Capacity Measured Via Maximum Heart Rate | Baseline to 1 Hour | A change in exercise capacity measured via maximum heart rate (in beats per minute). The measurement will be obtained from the Exercise Stress Test |
| The Change in Exercise Capacity Measured Via Minimum Oxygen Saturation Levels. | Baseline to 1 Hour | A change in exercise capacity measured via minimum oxygen saturation (%). The measurement will be obtained from the Exercise Stress Test |
| The Change in Exercise Capacity Measured Via Metabolic Equivalents of Task (METs). | Baseline to 1 hour | A change in exercise capacity measured via metabolic equivalents of task (METs). The measurement will be obtained from the Exercise Stress Test. One MET is defined as 3.5 mL 02 uptake/kg per minute |
Countries
United States
Participant flow
Pre-assignment details
One subject withdrew consent before being randomized and subsequent medication administered.
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Crossover to Placebo Sildenafil dosage (0.5mg/kg (max 20mg)) administered at the time of enrollment followed by a battery of exercise tests. After a washout period, the process will be repeated with the placebo drug administered before the exercises. | 8 |
| Placebo Crossover to Sidenafil Patient will receive a look-alike placebo administered at the time of enrollment followed by a battery of exercise tests. After a washout period, the process will be repeated with the Sildenafil dosage will be 0.5mg/kg (max 20mg) administered before the exercises. | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Sildenafil Crossover to Placebo | Placebo Crossover to Sidenafil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
The Change in Exercise Capacity Measured Via Exercise Time
A change in exercise capacity measured via exercise time (in minutes). The measurement will be obtained from the Exercise Stress Test
Time frame: baseline to 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Exercise Time | Placebo Time | 12.1 minutes | Standard Error 0.8 |
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Exercise Time | Sildenafil Time | 11.6 minutes | Standard Error 0.6 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Exercise Time | Placebo Time | 10.5 minutes | Standard Error 0.5 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Exercise Time | Sildenafil Time | 10.5 minutes | Standard Error 0.4 |
Primary
The Change in Exercise Capacity Measured Via Maximum Oxygen Consumed During Exercise (VO2)
A change in exercise capacity measured via maximum oxygen consumed during exercise (VO2). The measurement will be obtained from the Exercise Stress Test
Time frame: baseline to 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Maximum Oxygen Consumed During Exercise (VO2) | Sildenafil VO2 | 39.4 ml/min/kg | Standard Error 2.6 |
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Maximum Oxygen Consumed During Exercise (VO2) | Placebo VO2 | 41.2 ml/min/kg | Standard Error 3.4 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Maximum Oxygen Consumed During Exercise (VO2) | Sildenafil VO2 | 36.8 ml/min/kg | Standard Error 2.4 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Maximum Oxygen Consumed During Exercise (VO2) | Placebo VO2 | 34.4 ml/min/kg | Standard Error 2.8 |
Secondary
The Change in Exercise Capacity Measured Via Maximum Heart Rate
A change in exercise capacity measured via maximum heart rate (in beats per minute). The measurement will be obtained from the Exercise Stress Test
Time frame: Baseline to 1 Hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Maximum Heart Rate | Sildenafil Heart Rate | 182.3 beats per minute | Standard Error 6.4 |
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Maximum Heart Rate | Placebo Heart Rate | 182.6 beats per minute | Standard Error 7.2 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Maximum Heart Rate | Sildenafil Heart Rate | 175.4 beats per minute | Standard Error 6.9 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Maximum Heart Rate | Placebo Heart Rate | 167.8 beats per minute | Standard Error 7 |
Secondary
The Change in Exercise Capacity Measured Via Metabolic Equivalents of Task (METs).
A change in exercise capacity measured via metabolic equivalents of task (METs). The measurement will be obtained from the Exercise Stress Test. One MET is defined as 3.5 mL 02 uptake/kg per minute
Time frame: Baseline to 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Metabolic Equivalents of Task (METs). | Sildenafil Metabolic Equivalent | 13.6 Mets | Standard Error 0.7 |
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Metabolic Equivalents of Task (METs). | Placebo Metabolic Equivalent | 14.1 Mets | Standard Error 0.9 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Metabolic Equivalents of Task (METs). | Sildenafil Metabolic Equivalent | 12.4 Mets | Standard Error 0.5 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Metabolic Equivalents of Task (METs). | Placebo Metabolic Equivalent | 12.1 Mets | Standard Error 0.6 |
Secondary
The Change in Exercise Capacity Measured Via Minimum Oxygen Saturation Levels.
A change in exercise capacity measured via minimum oxygen saturation (%). The measurement will be obtained from the Exercise Stress Test
Time frame: Baseline to 1 Hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Minimum Oxygen Saturation Levels. | Sildenafil minimum oxygen saturation % | 94.1 Percentage of oxygen saturation | Standard Error 1 |
| Sildenafil Crossover to Placebo | The Change in Exercise Capacity Measured Via Minimum Oxygen Saturation Levels. | Placebo minimum oxygen saturation % | 93.1 Percentage of oxygen saturation | Standard Error 0.8 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Minimum Oxygen Saturation Levels. | Sildenafil minimum oxygen saturation % | 94.6 Percentage of oxygen saturation | Standard Error 0.7 |
| Placebo Crossover to Sidenafil | The Change in Exercise Capacity Measured Via Minimum Oxygen Saturation Levels. | Placebo minimum oxygen saturation % | 93.8 Percentage of oxygen saturation | Standard Error 0.6 |