Single Ventricle Heart Disease
Conditions
Keywords
Fontan, Maximal Oxygen Consumption, Vascular Function, EndoPAT, Myocardial Performance
Brief summary
This study will evaluate the clinical efficacy and safety of udenafil, an orally administered, potent and selective inhibitor of PDE5, versus placebo for the treatment of adolescent subjects who have undergone the Fontan procedure.
Detailed description
This study is a randomized, double-blinded, efficacy trial of the effects of udenafil vs. placebo on the background of standard therapy on maximal VO2 (ml/kg/min) from baseline to six months in adolescent survivors of the Fontan procedure. . The target sample size is 400 subjects (200 per group).
Interventions
DRUGUdenafil
Active drug
DRUGPlacebo
Matching Placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Mezzion Pharma Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment. 2. Participant consent or parental/guardian consent and participant assent 3. Participant fluency in primary language of country in which study is being conducted
Exclusion criteria
1. Weight \< 40 kg 2. Height \< 132 cm. 3. Hospitalization for acute decompensated heart failure within the last 12 months. 4. Current intravenous inotropic drugs. 5. Undergoing evaluation for heart transplantation or listed for transplantation. 6. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis. 7. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein stenosis resulting in a mean gradient of \> 4 mmHg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography, obtained prior to screening for the trial. 8. Single lung physiology with greater than 80% flow to one lung. 9. VO2 less than 50% 10. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment. 11. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment. 12. Significant renal (serum creatinine \> 2.0), hepatic (serum AST and/or ALT \> 3 times upper limit of normal), gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications, based on laboratory assessment six weeks prior to screening for the trial. 13. Inability to complete exercise testing at baseline screening. 14. History of PDE-5 inhibitor use within 3 months before study onset. 15. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset. 16. Known intolerance to oral udenafil. 17. Frequent use of medications or other substances that inhibit or induce CYP3A4. 18. Current use of alpha-blockers or nitrates. 19. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results. 20. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results. 21. Cardiac care, ongoing or planned, at a non-study center that would impede study completion. 22. For females: Pregnancy at the time of screening, pregnancy planned before study completion, or refusal to use an acceptable method of contraception for study duration if sexually active. 23. Unable to abstain or limit intake of grapefruit juice during the duration of the trial. 24. Refusal to provide written informed consent/assent. 25. In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF) | Baseline to 26 Weeks | The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26 | Week 26 | Endothelial pulse amplitude tonometry (Endo-PAT) is a technique for the non-invasive assessment of peripheral vascular function. In adults, Endo-PAT has been demonstrated to identify those with coronary artery dysfunction and to correlate with brachial artery reactivity testing. Endo-PAT use in children has been more limited, but has shown excellent reproducibility. Reactive hyperemia index, a measure of the hyperemic response adjusted for baseline blood flow, is a measure of vascular function. A higher value denotes better, or more healthy, vascular (endothelial) function. |
| Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26. | Week 26 | BNP is a hormone produced when the heart is enlarged or has to work harder to pump blood to the body. Higher levels of BNP can be a sign of heart failure. |
| Change in VO2 at VAT | 26 Weeks | This outcome measures the change in milliliters of oxygen consumption (VO2) per minute at the ventilatory anaerobic threshold (VAT) between Week 26 and Baseline Visits using last observation carried forward (ITT Population). The anaerobic threshold is the period in exercise when metabolism switches from aerobic to anaerobic. This is an useful measure of submaximal exercise capacity particularly in the single ventricle population. |
| Change in Work Rate at VAT From Baseline to Week 26 With LOCF | 26 Weeks | This outcome measures the change in work (measured in Watts) at the ventilatory anaerobic threshold (VAT) between Week 26 and Baseline Visits using last observation carried forward (ITT Population). The anaerobic threshold is the period in exercise when metabolism switches from aerobic to anaerobic. This is an useful measure of submaximal exercise capacity particularly in the single ventricle population. |
| Change in VE/VCO2 at VAT From Baseline to Week 26 | 26 Weeks | This measure is a ratio of the amount of inspired air required to clear a given volume of CO2 from the circulation at the ventilatory anaerobic threshold (VAT). This measurement is made during exercise stress testing. Decreases in this ratio may reflect an improvement in ventilatory efficiency or an improvement in cardiac function. |
| Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF | Week 26 | — |
| Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26 | Week 26 | The amount of air that enters the lungs per minute at maximal exercise effort. |
| Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF | Week 26 | Change in power at maximal exercise effort. |
| Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported) | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported) | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Myocardial Performance Index (MPI) From Baseline to Week 26 | Week 26 | Change in the myocardial performance index (MPI) from baseline to 26 weeks is determined by velocities from blood pool Doppler of the inflow and outflow tract of the dominant ventricle. The measure is the ratio of the sum of isovolumetric contraction time and isovolumetric relaxation time, divided by ventricular ejection time. A lower value is consistent with a more efficient ventricle (better function). A value of zero indicates that there is no isovolumetric contraction or relaxation and, while physiologically implausible, would be consistent with a perfectly efficient ventricle. The mean left ventricular MPI in healthy people without heart disease is approximately 0.35 while the mean right ventricular MPI is approximately 0.1 due to the reduced ventricular afterload of the pulmonary circulation. In general, a decrease in the MPI corresponds to more efficient (better) ventricular function, while an increase in MPI corresponds to less efficient (worse) ventricular function. |
| Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported) | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported) | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 week. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported) | 26 weeks | The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported) | 26 weeks | The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported) | 26 weeks | The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported) | 26 weeks | The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
| Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported) | 26 weeks | The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline). |
Countries
Canada, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug Udenafil. One tablet twice daily for 26 weeks
Udenafil: Active drug | 200 |
| Placebo Placebo. One tablet twice daily for 26 weeks
Placebo: Matching Placebo | 200 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Drug | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 15.4 years STANDARD_DEVIATION 2.033 | 15.6 years STANDARD_DEVIATION 1.978 | 15.5 years STANDARD_DEVIATION 2.005 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 25 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 168 Participants | 174 Participants | 342 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Log-transformed B-type natriuretic peptide (BNP) | 2.45 log(pg/mL) STANDARD_DEVIATION 1.003 | 2.26 log(pg/mL) STANDARD_DEVIATION 1.14 | 2.36 log(pg/mL) STANDARD_DEVIATION 1.076 |
| Log-transformed Reactive Hyperemia Index (lnRHI) | 0.46 Natural log-transformed RHI (lnRHI) STANDARD_DEVIATION 0.25 | 0.46 Natural log-transformed RHI (lnRHI) STANDARD_DEVIATION 0.332 | 0.46 Natural log-transformed RHI (lnRHI) STANDARD_DEVIATION 0.2936 |
| Maximal V02 at ventilatory anaerobic threshold (VAT) | 18.35 mL/kig/min STANDARD_DEVIATION 4.633 | 17.71 mL/kig/min STANDARD_DEVIATION 4.304 | 18.02 mL/kig/min STANDARD_DEVIATION 4.471 |
| Minute ventilation at maximal exercise effort | 70.65 L/min STANDARD_DEVIATION 21.055 | 75.84 L/min STANDARD_DEVIATION 22.323 | 73.25 L/min STANDARD_DEVIATION 21.828 |
| Myocardial Performance Index (MPI) | 0.45 Ratio STANDARD_DEVIATION 0.172 | 0.45 Ratio STANDARD_DEVIATION 0.154 | 0.45 Ratio STANDARD_DEVIATION 0.163 |
| PCQLI Total Score-Ages 13 to 18-Child reported | 73.39 Scores on a scale STANDARD_DEVIATION 14.979 | 73.62 Scores on a scale STANDARD_DEVIATION 14.79 | 73.51 Scores on a scale STANDARD_DEVIATION 14.86 |
| PCQLI Total Score-Ages 13 to 18-Parent reported | 70.23 Scores on a scale STANDARD_DEVIATION 15.001 | 72.74 Scores on a scale STANDARD_DEVIATION 15.97 | 71.54 Scores on a scale STANDARD_DEVIATION 15.541 |
| PCQLI Total Score-Ages 8 to 12-Parent reported | 65.56 Scores on a scale STANDARD_DEVIATION 18.078 | 70.27 Scores on a scale STANDARD_DEVIATION 16.809 | 67.36 Scores on a scale STANDARD_DEVIATION 17.57 |
| Peak VO2 | 27.84 mL/kg/min STANDARD_DEVIATION 6.877 | 28.01 mL/kg/min STANDARD_DEVIATION 6.128 | 27.92 mL/kg/min STANDARD_DEVIATION 6.5 |
| Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12-Child reported | 69.04 Scores on a scale STANDARD_DEVIATION 15.091 | 75.55 Scores on a scale STANDARD_DEVIATION 14.392 | 71.67 Scores on a scale STANDARD_DEVIATION 15.005 |
| Pediatric Quality of Life Inventory (PedsQL) General Core Scale-Physical Functioning-Child reported | 72.52 Scores on a scale STANDARD_DEVIATION 16.805 | 73.35 Scores on a scale STANDARD_DEVIATION 16.686 | 72.94 Scores on a scale STANDARD_DEVIATION 16.729 |
| PedsQL Cardiac Module Scale-Cognitive Problems | 64.67 Scores on a scale STANDARD_DEVIATION 20.709 | 65.23 Scores on a scale STANDARD_DEVIATION 22.967 | 64.95 Scores on a scale STANDARD_DEVIATION 21.85 |
| PedsQL Cardiac Module Scale-Communication Problems | 74.74 Scores on a scale STANDARD_DEVIATION 21.933 | 72.63 Scores on a scale STANDARD_DEVIATION 22.938 | 73.67 Scores on a scale STANDARD_DEVIATION 22.443 |
| PedsQL Cardiac Module Scale-Perceived Physical Appearance | 74.23 Scores on a scale STANDARD_DEVIATION 24.291 | 75.92 Scores on a scale STANDARD_DEVIATION 25.185 | 75.09 Scores on a scale STANDARD_DEVIATION 24.731 |
| PedsQL Cardiac Module Scale-Treatment Anxiety | 79.99 Scores on a scale STANDARD_DEVIATION 23.164 | 80.09 Scores on a scale STANDARD_DEVIATION 23.736 | 80.04 Scores on a scale STANDARD_DEVIATION 23.426 |
| PedsQL Cardiac Module Scale-Treatment II | 87.84 Scores on a scale STANDARD_DEVIATION 9.769 | 89.35 Scores on a scale STANDARD_DEVIATION 9.288 | 88.61 Scores on a scale STANDARD_DEVIATION 9.544 |
| PedsQL General Core Scale-Physical Functioning-Parent reported | 71.58 Scores on a scale STANDARD_DEVIATION 18.155 | 73.18 Scores on a scale STANDARD_DEVIATION 18.006 | 72.38 Scores on a scale STANDARD_DEVIATION 18.075 |
| PedsQL General Core Scale-Psychosocial Health Summary Score-Child reported | 71.90 Scores on a scale STANDARD_DEVIATION 16.976 | 72.30 Scores on a scale STANDARD_DEVIATION 16.811 | 72.10 Scores on a scale STANDARD_DEVIATION 16.872 |
| PedsQL General Core Scale-Psychosocial Health Summary Score-Parent reported | 68.48 Scores on a scale STANDARD_DEVIATION 16.13 | 70.51 Scores on a scale STANDARD_DEVIATION 17.525 | 69.49 Scores on a scale STANDARD_DEVIATION 16.849 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 21 Participants | 38 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 13 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 9 Participants | 11 Participants |
| Race (NIH/OMB) White | 169 Participants | 155 Participants | 324 Participants |
| Region of Enrollment Canada | 8 participants | 11 participants | 19 participants |
| Region of Enrollment South Korea | 14 participants | 19 participants | 33 participants |
| Region of Enrollment United States | 178 participants | 170 participants | 348 participants |
| Respiratory rate at maximal exercise effort | 51.11 Breaths per minute STANDARD_DEVIATION 11.257 | 51.35 Breaths per minute STANDARD_DEVIATION 12.676 | 51.23 Breaths per minute STANDARD_DEVIATION 11.975 |
| Sex: Female, Male Female | 89 Participants | 72 Participants | 161 Participants |
| Sex: Female, Male Male | 111 Participants | 128 Participants | 239 Participants |
| Ventilatory equivalents of carbon dioxide (VE/VCO2) at VAT | 34.32 Ratio STANDARD_DEVIATION 4.845 | 34.75 Ratio STANDARD_DEVIATION 5.157 | 34.54 Ratio STANDARD_DEVIATION 5.006 |
| Weight | 57.1 kg STANDARD_DEVIATION 13.925 | 59.0 kg STANDARD_DEVIATION 13.187 | 58.1 kg STANDARD_DEVIATION 13.577 |
| Work rate at maximal exercise effort | 119.68 Watts STANDARD_DEVIATION 32.176 | 123.11 Watts STANDARD_DEVIATION 32.14 | 121.40 Watts STANDARD_DEVIATION 32.163 |
| Work rate at ventilatory anaerobic threshold (VAT) | 66.19 Watts STANDARD_DEVIATION 26.321 | 66.10 Watts STANDARD_DEVIATION 23.446 | 66.14 Watts STANDARD_DEVIATION 24.847 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 200 | 0 / 200 |
| other Total, other adverse events | 158 / 200 | 135 / 200 |
| serious Total, serious adverse events | 14 / 200 | 10 / 200 |
Outcome results
Primary
Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF)
The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks
Time frame: Baseline to 26 Weeks
Population: Intent to Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF) | -0.23 mL/kg/min | Standard Deviation 4.056 |
| Placebo | Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF) | -0.89 mL/kg/min | Standard Deviation 3.672 |
Comparison: It was estimated that a sample size of 198 participants per group would provide 90% power to detect a mean treatment group difference in change from baseline to Week 26 in maximal VO2 scores of 10% (ie, an improvement of 2.8 mL/kg/min in the udenafil group compared to 0 in the control group, assuming a Type I error of 0.05 and standard deviation of 7.235). A difference of 2.8, equivalent to a 10% increase from a baseline of 28 mL/kg/min, represents approximately 0.4 standard deviations.p-value: 0.092ANCOVA
Secondary
Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26
Endothelial pulse amplitude tonometry (Endo-PAT) is a technique for the non-invasive assessment of peripheral vascular function. In adults, Endo-PAT has been demonstrated to identify those with coronary artery dysfunction and to correlate with brachial artery reactivity testing. Endo-PAT use in children has been more limited, but has shown excellent reproducibility. Reactive hyperemia index, a measure of the hyperemic response adjusted for baseline blood flow, is a measure of vascular function. A higher value denotes better, or more healthy, vascular (endothelial) function.
Time frame: Week 26
Population: This analysis was performed only on participants with paired data. For variety of technical reasons the signal for the reactive hyperemia index was not sufficient to allow for accurate assessment of the index in a subset of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26 | 0.06 Natural log-transformed RHI (lnRHI) | Standard Deviation 0.301 |
| Placebo | Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26 | 0.04 Natural log-transformed RHI (lnRHI) | Standard Deviation 0.364 |
p-value: 0.591ANCOVA
Secondary
Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26
The amount of air that enters the lungs per minute at maximal exercise effort.
Time frame: Week 26
Population: ITT Population. Of note, some participants may not have had baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back to complete Week 26 assessments. Only participants with both a baseline value and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26 | 1.15 L/min | Standard Deviation 13.934 |
| Placebo | Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26 | -0.10 L/min | Standard Deviation 13.748 |
p-value: 0.915ANCOVA
Secondary
Change in Myocardial Performance Index (MPI) From Baseline to Week 26
Change in the myocardial performance index (MPI) from baseline to 26 weeks is determined by velocities from blood pool Doppler of the inflow and outflow tract of the dominant ventricle. The measure is the ratio of the sum of isovolumetric contraction time and isovolumetric relaxation time, divided by ventricular ejection time. A lower value is consistent with a more efficient ventricle (better function). A value of zero indicates that there is no isovolumetric contraction or relaxation and, while physiologically implausible, would be consistent with a perfectly efficient ventricle. The mean left ventricular MPI in healthy people without heart disease is approximately 0.35 while the mean right ventricular MPI is approximately 0.1 due to the reduced ventricular afterload of the pulmonary circulation. In general, a decrease in the MPI corresponds to more efficient (better) ventricular function, while an increase in MPI corresponds to less efficient (worse) ventricular function.
Time frame: Week 26
Population: This analysis was performed only on participants with paired data. For variety of technical reasons the quality of echocardiographic images were not sufficient to allow for accurate assessment of the MPI in a subset of participants. These reasons include poor acoustic windows and noisy Doppler signal.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Myocardial Performance Index (MPI) From Baseline to Week 26 | -0.02 ratio | Standard Deviation 0.112 |
| Placebo | Change in Myocardial Performance Index (MPI) From Baseline to Week 26 | 0.01 ratio | Standard Deviation 0.132 |
p-value: 0.024ANCOVA
Secondary
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants aged 13-18 with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported) | -0.08 Scores on a scale | Standard Deviation 11.032 |
| Placebo | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported) | 0.09 Scores on a scale | Standard Deviation 9.626 |
p-value: 0.963ANCOVA
Secondary
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only parents of participants aged 13-18 with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported) | 0.36 Scores on a scale | Standard Deviation 11.722 |
| Placebo | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported) | -1.60 Scores on a scale | Standard Deviation 11.179 |
p-value: 0.246ANCOVA
Secondary
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value who were aged 8 to 12 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported) | 3.26 Scores on a scale | Standard Deviation 12.287 |
| Placebo | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported) | -2.37 Scores on a scale | Standard Deviation 16.368 |
p-value: 0.533ANCOVA
Secondary
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis. Only parents with participants aged 8-12 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported) | -0.91 Scores on a scale | Standard Deviation 13.399 |
| Placebo | Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported) | -4.44 Scores on a scale | Standard Deviation 6.389 |
p-value: 0.654ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported) | 2.08 Scores on a scale | Standard Deviation 12.006 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported) | 1.53 Scores on a scale | Standard Deviation 11.823 |
p-value: 0.691ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported) | 2.74 Scores on a scale | Standard Deviation 18.011 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported) | 1.94 Scores on a scale | Standard Deviation 15.328 |
p-value: 0.985ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported) | 2.84 Scores on a scale | Standard Deviation 11.356 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported) | 1.74 Scores on a scale | Standard Deviation 10.7 |
p-value: 0.273ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported) | 2.64 Scores on a scale | Standard Deviation 13.546 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported) | 2.15 Scores on a scale | Standard Deviation 13.737 |
p-value: 0.966ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale | 2.19 Scores on a scale | Standard Deviation 16.826 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale | 3.05 Scores on a scale | Standard Deviation 17.027 |
p-value: 0.543ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 week. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale | 1.82 Scores on a scale | Standard Deviation 20.406 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale | 4.36 Scores on a scale | Standard Deviation 17.954 |
p-value: 0.352ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale | 2.45 Scores on a scale | Standard Deviation 20.819 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale | 0.78 Scores on a scale | Standard Deviation 17.396 |
p-value: 0.382ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale | 3.37 Scores on a scale | Standard Deviation 19.258 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale | 1.66 Scores on a scale | Standard Deviation 16.477 |
p-value: 0.236ANCOVA
Secondary
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Time frame: 26 weeks
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back and complete the Week 26 assessments. Only participants with both a Baseline and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported) | 0.24 Scores on a scale | Standard Deviation 11.655 |
| Placebo | Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported) | -0.09 Scores on a scale | Standard Deviation 9.046 |
p-value: 0.706ANCOVA
Secondary
Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF
Time frame: Week 26
Population: ITT Population. Of note, some participants may not have had Baseline values due to errors in data capture and/or the participant did not complete the assessment, but was encouraged to come back to complete Week 26 assessments. Only participants with both a Baseline value and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF | -1.01 Breaths/min | Standard Deviation 10.03 |
| Placebo | Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF | -1.44 Breaths/min | Standard Deviation 9.928 |
p-value: 0.696ANCOVA
Secondary
Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26.
BNP is a hormone produced when the heart is enlarged or has to work harder to pump blood to the body. Higher levels of BNP can be a sign of heart failure.
Time frame: Week 26
Population: This analysis was performed on a subset of patients who had analyzable lab samples at both baseline and 26 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26. | 0.08 pg/mL | Standard Deviation 0.905 |
| Placebo | Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26. | 0.03 pg/mL | Standard Deviation 1.137 |
p-value: 0.169ANCOVA
Secondary
Change in VE/VCO2 at VAT From Baseline to Week 26
This measure is a ratio of the amount of inspired air required to clear a given volume of CO2 from the circulation at the ventilatory anaerobic threshold (VAT). This measurement is made during exercise stress testing. Decreases in this ratio may reflect an improvement in ventilatory efficiency or an improvement in cardiac function.
Time frame: 26 Weeks
Population: Data from the anaerobic threshold is not calculable for all participants given noise within the data tracings. These data are from the intent to treat (ITT) analyses for all participants for whom a baseline value was calculable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in VE/VCO2 at VAT From Baseline to Week 26 | -0.76 Ratio | Standard Deviation 3.564 |
| Placebo | Change in VE/VCO2 at VAT From Baseline to Week 26 | -0.05 Ratio | Standard Deviation 2.967 |
p-value: 0.011ANCOVA
Secondary
Change in VO2 at VAT
This outcome measures the change in milliliters of oxygen consumption (VO2) per minute at the ventilatory anaerobic threshold (VAT) between Week 26 and Baseline Visits using last observation carried forward (ITT Population). The anaerobic threshold is the period in exercise when metabolism switches from aerobic to anaerobic. This is an useful measure of submaximal exercise capacity particularly in the single ventricle population.
Time frame: 26 Weeks
Population: Data from the anaerobic threshold is not calculable for all participants given noise within the data tracings. These data are from the intent to treat (ITT) analyses for all participants for whom a baseline value was calculable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in VO2 at VAT | -0.07 mL/kg/min | Standard Deviation 2.998 |
| Placebo | Change in VO2 at VAT | -0.68 mL/kg/min | Standard Deviation 3.216 |
p-value: 0.012ANCOVA
Secondary
Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF
Change in power at maximal exercise effort.
Time frame: Week 26
Population: ITT Population. Of note, some participants may not have had baseline values due to errors in data capture and/or not completing the assessment, but were encouraged to come back to complete Week 26 assessments. Only participants with both a baseline value and a Week 26 value were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF | 2.99 Watts | Standard Deviation 14.334 |
| Placebo | Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF | 2.45 Watts | Standard Deviation 13.503 |
Comparison: LS mean differences between treatment groups were analyzed.p-value: 0.891ANCOVA
Secondary
Change in Work Rate at VAT From Baseline to Week 26 With LOCF
This outcome measures the change in work (measured in Watts) at the ventilatory anaerobic threshold (VAT) between Week 26 and Baseline Visits using last observation carried forward (ITT Population). The anaerobic threshold is the period in exercise when metabolism switches from aerobic to anaerobic. This is an useful measure of submaximal exercise capacity particularly in the single ventricle population.
Time frame: 26 Weeks
Population: Data from the anaerobic threshold is not calculable for all participants given noise within the data tracings. These data are from the intent to treat (ITT) analyses for all participants for whom a baseline value was calculable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Udenafil | Change in Work Rate at VAT From Baseline to Week 26 With LOCF | 3.46 Watts | Standard Deviation 15.076 |
| Placebo | Change in Work Rate at VAT From Baseline to Week 26 With LOCF | 0.31 Watts | Standard Deviation 13.246 |
p-value: 0.029ANCOVA