Trial Outcomes & Findings for Fontan Udenafil Exercise Longitudinal Assessment Trial (NCT NCT02741115)

NCT ID: NCT02741115

Last Updated: 2025-06-17

Results Overview

The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

400 participants

Primary outcome timeframe

Baseline to 26 Weeks

Results posted on

2025-06-17

Participant Flow

Participant milestones

Participant milestones
Measure	Drug Udenafil. One tablet twice daily for 26 weeks Udenafil: Active drug	Placebo Placebo. One tablet twice daily for 26 weeks Placebo: Matching Placebo
Overall Study STARTED	200	200
Overall Study COMPLETED	188	194
Overall Study NOT COMPLETED	12	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Drug Udenafil. One tablet twice daily for 26 weeks Udenafil: Active drug	Placebo Placebo. One tablet twice daily for 26 weeks Placebo: Matching Placebo
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	7	4
Overall Study Withdrawal by Subject	4	2

Baseline Characteristics

Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline to 26 Weeks

Population: Intent to Treat Population

The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=200 Participants Intent to Treat Population on active drug.	Placebo n=200 Participants Intent to Treat Population on Placebo
Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF)	-0.23 mL/kg/min Standard Deviation 4.056	-0.89 mL/kg/min Standard Deviation 3.672

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Udenafil n=122 Participants Intent to Treat Population on active drug.	Placebo n=128 Participants Intent to Treat Population on Placebo
Change in Myocardial Performance Index (MPI) From Baseline to Week 26	-0.02 ratio Standard Deviation 0.112	0.01 ratio Standard Deviation 0.132

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Udenafil n=175 Participants Intent to Treat Population on active drug.	Placebo n=184 Participants Intent to Treat Population on Placebo
Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26	0.06 Natural log-transformed RHI (lnRHI) Standard Deviation 0.301	0.04 Natural log-transformed RHI (lnRHI) Standard Deviation 0.364

SECONDARY outcome

Timeframe: Week 26

Population: This analysis was performed on a subset of patients who had analyzable lab samples at both baseline and 26 weeks.

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.

Outcome measures

Outcome measures
Measure	Udenafil n=187 Participants Intent to Treat Population on active drug.	Placebo n=191 Participants Intent to Treat Population on Placebo
Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26.	0.08 pg/mL Standard Deviation 0.905	0.03 pg/mL Standard Deviation 1.137

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Udenafil n=170 Participants Intent to Treat Population on active drug.	Placebo n=181 Participants Intent to Treat Population on Placebo
Change in VO2 at VAT	-0.07 mL/kg/min Standard Deviation 2.998	-0.68 mL/kg/min Standard Deviation 3.216

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Udenafil n=167 Participants Intent to Treat Population on active drug.	Placebo n=177 Participants Intent to Treat Population on Placebo
Change in Work Rate at VAT From Baseline to Week 26 With LOCF	3.46 Watts Standard Deviation 15.076	0.31 Watts Standard Deviation 13.246

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Udenafil n=170 Participants Intent to Treat Population on active drug.	Placebo n=181 Participants Intent to Treat Population on Placebo
Change in VE/VCO2 at VAT From Baseline to Week 26	-0.76 Ratio Standard Deviation 3.564	-0.05 Ratio Standard Deviation 2.967

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Udenafil n=199 Participants Intent to Treat Population on active drug.	Placebo n=200 Participants Intent to Treat Population on Placebo
Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF	-1.01 Breaths/min Standard Deviation 10.030	-1.44 Breaths/min Standard Deviation 9.928

SECONDARY outcome

Timeframe: 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.

The amount of air that enters the lungs per minute at maximal exercise effort.

Outcome measures

Outcome measures
Measure	Udenafil n=199 Participants Intent to Treat Population on active drug.	Placebo n=200 Participants Intent to Treat Population on Placebo
Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26	1.15 L/min Standard Deviation 13.934	-0.10 L/min Standard Deviation 13.748

SECONDARY outcome

Timeframe: Week 26

Change in power at maximal exercise effort.

Outcome measures

Outcome measures
Measure	Udenafil n=198 Participants Intent to Treat Population on active drug.	Placebo n=199 Participants Intent to Treat Population on Placebo
Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF	2.99 Watts Standard Deviation 14.334	2.45 Watts Standard Deviation 13.503

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Udenafil n=186 Participants Intent to Treat Population on active drug.	Placebo n=193 Participants Intent to Treat Population on Placebo
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	1.53 Scores on a scale Standard Deviation 11.823

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=181 Participants Intent to Treat Population on active drug.	Placebo n=181 Participants Intent to Treat Population on Placebo
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	1.94 Scores on a scale Standard Deviation 15.328

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=185 Participants Intent to Treat Population on active drug.	Placebo n=193 Participants Intent to Treat Population on Placebo
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	1.74 Scores on a scale Standard Deviation 10.700

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=181 Participants Intent to Treat Population on active drug.	Placebo n=181 Participants Intent to Treat Population on Placebo
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	2.15 Scores on a scale Standard Deviation 13.737

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=164 Participants Intent to Treat Population on active drug.	Placebo n=173 Participants Intent to Treat Population on Placebo
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	-0.09 Scores on a scale Standard Deviation 9.046

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=184 Participants Intent to Treat Population on active drug.	Placebo n=192 Participants Intent to Treat Population on Placebo
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	0.78 Scores on a scale Standard Deviation 17.396

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=184 Participants Intent to Treat Population on active drug.	Placebo n=192 Participants Intent to Treat Population on Placebo
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale	3.37 Scores on a scale Standard Deviation 19.258	1.66 Scores on a scale Standard Deviation 16.477

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=183 Participants Intent to Treat Population on active drug.	Placebo n=192 Participants Intent to Treat Population on Placebo
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale	2.19 Scores on a scale Standard Deviation 16.826	3.05 Scores on a scale Standard Deviation 17.027

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Udenafil n=183 Participants Intent to Treat Population on active drug.	Placebo n=192 Participants Intent to Treat Population on Placebo
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale	1.82 Scores on a scale Standard Deviation 20.406	4.36 Scores on a scale Standard Deviation 17.954

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Udenafil n=16 Participants Intent to Treat Population on active drug.	Placebo n=12 Participants Intent to Treat Population on Placebo
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	-2.37 Scores on a scale Standard Deviation 16.368

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Udenafil n=17 Participants Intent to Treat Population on active drug.	Placebo n=11 Participants Intent to Treat Population on Placebo
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	-4.44 Scores on a scale Standard Deviation 6.389

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Udenafil n=158 Participants Intent to Treat Population on active drug.	Placebo n=170 Participants Intent to Treat Population on Placebo
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	0.09 Scores on a scale Standard Deviation 9.626

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Udenafil n=152 Participants Intent to Treat Population on active drug.	Placebo n=162 Participants Intent to Treat Population on Placebo
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	-1.60 Scores on a scale Standard Deviation 11.179

Adverse Events

Drug

Serious events: 14 serious events

Other events: 158 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 135 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Drug n=200 participants at risk Udenafil. One tablet twice daily for 26 weeks Udenafil: Active drug	Placebo n=200 participants at risk Placebo. One tablet twice daily for 26 weeks Placebo: Matching Placebo
Gastrointestinal disorders Nausea	8.0% 16/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	4.5% 9/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Gastrointestinal disorders Vomiting	7.5% 15/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	2.5% 5/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
General disorders Chest Pain	4.5% 9/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	8.0% 16/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Infections and infestations Nasopharyngitis	6.5% 13/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	4.5% 9/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Infections and infestations Upper Respiratory Tract Infectins	12.0% 24/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	11.0% 22/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Dizziness	8.0% 16/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	8.5% 17/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Headache	39.5% 79/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	25.5% 51/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.5% 21/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	2.5% 5/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Vascular disorders Flushing	16.0% 32/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	6.0% 12/200 • Number of events 200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.

Additional Information

Director of Clinical Trials

Mezzion Pharmaceuticals, Inc

Phone: 5734342579

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Drug n=200 Participants Udenafil. One tablet twice daily for 26 weeks Udenafil: Active drug	Placebo n=200 Participants Placebo. One tablet twice daily for 26 weeks Placebo: Matching Placebo	Total n=400 Participants Total of all reporting groups
Age, Continuous	15.4 years STANDARD_DEVIATION 2.033 • n=200 Participants	15.6 years STANDARD_DEVIATION 1.978 • n=200 Participants	15.5 years STANDARD_DEVIATION 2.005 • n=400 Participants
Sex: Female, Male Female	89 Participants n=200 Participants	72 Participants n=200 Participants	161 Participants n=400 Participants
Sex: Female, Male Male	111 Participants n=200 Participants	128 Participants n=200 Participants	239 Participants n=400 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=200 Participants	25 Participants n=200 Participants	56 Participants n=400 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	168 Participants n=200 Participants	174 Participants n=200 Participants	342 Participants n=400 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=200 Participants	1 Participants n=200 Participants	2 Participants n=400 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=200 Participants	0 Participants n=200 Participants	0 Participants n=400 Participants
Race (NIH/OMB) Asian	17 Participants n=200 Participants	21 Participants n=200 Participants	38 Participants n=400 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=200 Participants	0 Participants n=200 Participants	0 Participants n=400 Participants
Race (NIH/OMB) Black or African American	10 Participants n=200 Participants	13 Participants n=200 Participants	23 Participants n=400 Participants
Race (NIH/OMB) White	169 Participants n=200 Participants	155 Participants n=200 Participants	324 Participants n=400 Participants
Race (NIH/OMB) More than one race	2 Participants n=200 Participants	2 Participants n=200 Participants	4 Participants n=400 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=200 Participants	9 Participants n=200 Participants	11 Participants n=400 Participants
Region of Enrollment Canada	8 participants n=200 Participants	11 participants n=200 Participants	19 participants n=400 Participants
Region of Enrollment South Korea	14 participants n=200 Participants	19 participants n=200 Participants	33 participants n=400 Participants
Region of Enrollment United States	178 participants n=200 Participants	170 participants n=200 Participants	348 participants n=400 Participants
Peak VO2	27.84 mL/kg/min STANDARD_DEVIATION 6.877 • n=200 Participants	28.01 mL/kg/min STANDARD_DEVIATION 6.128 • n=200 Participants	27.92 mL/kg/min STANDARD_DEVIATION 6.50 • n=400 Participants
Weight	57.1 kg STANDARD_DEVIATION 13.925 • n=200 Participants	59.0 kg STANDARD_DEVIATION 13.187 • n=200 Participants	58.1 kg STANDARD_DEVIATION 13.577 • n=400 Participants
Maximal V02 at ventilatory anaerobic threshold (VAT)	18.35 mL/kig/min STANDARD_DEVIATION 4.633 • n=170 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	17.71 mL/kig/min STANDARD_DEVIATION 4.304 • n=181 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	18.02 mL/kig/min STANDARD_DEVIATION 4.471 • n=351 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Ventilatory equivalents of carbon dioxide (VE/VCO2) at VAT	34.32 Ratio STANDARD_DEVIATION 4.845 • n=170 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	34.75 Ratio STANDARD_DEVIATION 5.157 • n=181 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	34.54 Ratio STANDARD_DEVIATION 5.006 • n=351 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Respiratory rate at maximal exercise effort	51.11 Breaths per minute STANDARD_DEVIATION 11.257 • n=199 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	51.35 Breaths per minute STANDARD_DEVIATION 12.676 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	51.23 Breaths per minute STANDARD_DEVIATION 11.975 • n=399 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Minute ventilation at maximal exercise effort	70.65 L/min STANDARD_DEVIATION 21.055 • n=199 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	75.84 L/min STANDARD_DEVIATION 22.323 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	73.25 L/min STANDARD_DEVIATION 21.828 • n=399 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Work rate at maximal exercise effort	119.68 Watts STANDARD_DEVIATION 32.176 • n=198 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	123.11 Watts STANDARD_DEVIATION 32.140 • n=199 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	121.40 Watts STANDARD_DEVIATION 32.163 • n=397 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Work rate at ventilatory anaerobic threshold (VAT)	66.19 Watts STANDARD_DEVIATION 26.321 • n=167 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	66.10 Watts STANDARD_DEVIATION 23.446 • n=177 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	66.14 Watts STANDARD_DEVIATION 24.847 • n=344 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Myocardial Performance Index (MPI)	0.45 Ratio STANDARD_DEVIATION 0.172 • n=150 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	0.45 Ratio STANDARD_DEVIATION 0.154 • n=155 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	0.45 Ratio STANDARD_DEVIATION 0.163 • n=305 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Log-transformed Reactive Hyperemia Index (lnRHI)	0.46 Natural log-transformed RHI (lnRHI) STANDARD_DEVIATION 0.250 • n=191 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	0.46 Natural log-transformed RHI (lnRHI) STANDARD_DEVIATION 0.332 • n=192 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	0.46 Natural log-transformed RHI (lnRHI) STANDARD_DEVIATION 0.2936 • n=383 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Log-transformed B-type natriuretic peptide (BNP)	2.45 log(pg/mL) STANDARD_DEVIATION 1.003 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	2.26 log(pg/mL) STANDARD_DEVIATION 1.140 • n=199 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	2.36 log(pg/mL) STANDARD_DEVIATION 1.076 • n=399 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
Pediatric Quality of Life Inventory (PedsQL) General Core Scale-Physical Functioning-Child reported	72.52 Scores on a scale STANDARD_DEVIATION 16.805 • n=196 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	73.35 Scores on a scale STANDARD_DEVIATION 16.686 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	72.94 Scores on a scale STANDARD_DEVIATION 16.729 • n=396 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL General Core Scale-Physical Functioning-Parent reported	71.58 Scores on a scale STANDARD_DEVIATION 18.155 • n=194 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	73.18 Scores on a scale STANDARD_DEVIATION 18.006 • n=193 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	72.38 Scores on a scale STANDARD_DEVIATION 18.075 • n=387 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL General Core Scale-Psychosocial Health Summary Score-Child reported	71.90 Scores on a scale STANDARD_DEVIATION 16.976 • n=196 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	72.30 Scores on a scale STANDARD_DEVIATION 16.811 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	72.10 Scores on a scale STANDARD_DEVIATION 16.872 • n=396 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL General Core Scale-Psychosocial Health Summary Score-Parent reported	68.48 Scores on a scale STANDARD_DEVIATION 16.130 • n=194 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	70.51 Scores on a scale STANDARD_DEVIATION 17.525 • n=193 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	69.49 Scores on a scale STANDARD_DEVIATION 16.849 • n=387 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL Cardiac Module Scale-Treatment II	87.84 Scores on a scale STANDARD_DEVIATION 9.769 • n=178 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	89.35 Scores on a scale STANDARD_DEVIATION 9.288 • n=185 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	88.61 Scores on a scale STANDARD_DEVIATION 9.544 • n=363 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL Cardiac Module Scale-Perceived Physical Appearance	74.23 Scores on a scale STANDARD_DEVIATION 24.291 • n=195 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	75.92 Scores on a scale STANDARD_DEVIATION 25.185 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	75.09 Scores on a scale STANDARD_DEVIATION 24.731 • n=395 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL Cardiac Module Scale-Treatment Anxiety	79.99 Scores on a scale STANDARD_DEVIATION 23.164 • n=194 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	80.09 Scores on a scale STANDARD_DEVIATION 23.736 • n=200 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	80.04 Scores on a scale STANDARD_DEVIATION 23.426 • n=394 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL Cardiac Module Scale-Cognitive Problems	64.67 Scores on a scale STANDARD_DEVIATION 20.709 • n=195 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	65.23 Scores on a scale STANDARD_DEVIATION 22.967 • n=198 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	64.95 Scores on a scale STANDARD_DEVIATION 21.850 • n=393 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
PedsQL Cardiac Module Scale-Communication Problems	74.74 Scores on a scale STANDARD_DEVIATION 21.933 • n=195 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	72.63 Scores on a scale STANDARD_DEVIATION 22.938 • n=199 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.	73.67 Scores on a scale STANDARD_DEVIATION 22.443 • n=394 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment.
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 • n=28 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only participants aged 8 to 12 were included in this assessment.	75.55 Scores on a scale STANDARD_DEVIATION 14.392 • n=19 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only participants aged 8 to 12 were included in this assessment.	71.67 Scores on a scale STANDARD_DEVIATION 15.005 • n=47 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only participants aged 8 to 12 were included in this assessment.
PCQLI Total Score-Ages 8 to 12-Parent reported	65.56 Scores on a scale STANDARD_DEVIATION 18.078 • n=29 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only parents with participants aged 8 to 12 were included in this assessment.	70.27 Scores on a scale STANDARD_DEVIATION 16.809 • n=18 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only parents with participants aged 8 to 12 were included in this assessment.	67.36 Scores on a scale STANDARD_DEVIATION 17.570 • n=47 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only parents with participants aged 8 to 12 were included in this assessment.
PCQLI Total Score-Ages 13 to 18-Child reported	73.39 Scores on a scale STANDARD_DEVIATION 14.979 • n=167 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only participants aged 13 to 18 were included in this assessment.	73.62 Scores on a scale STANDARD_DEVIATION 14.790 • n=179 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only participants aged 13 to 18 were included in this assessment.	73.51 Scores on a scale STANDARD_DEVIATION 14.860 • n=346 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only participants aged 13 to 18 were included in this assessment.
PCQLI Total Score-Ages 13 to 18-Parent reported	70.23 Scores on a scale STANDARD_DEVIATION 15.001 • n=163 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only parents of participants aged 13 to 18 were included in this assessment.	72.74 Scores on a scale STANDARD_DEVIATION 15.970 • n=177 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only parents of participants aged 13 to 18 were included in this assessment.	71.54 Scores on a scale STANDARD_DEVIATION 15.541 • n=340 Participants • Not all participants had a Baseline value due to errors in data capture and/or the participant did not complete the assessment. Only parents of participants aged 13 to 18 were included in this assessment.

Measure	Drug n=200 participants at risk Udenafil. One tablet twice daily for 26 weeks Udenafil: Active drug	Placebo n=200 participants at risk Placebo. One tablet twice daily for 26 weeks Placebo: Matching Placebo
Eye disorders Retinal Artery Thrombosis	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Diplegia	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.0% 2/200 • Number of events 3 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Palpitation	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Syncope	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	1.0% 2/200 • Number of events 2 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Respiratory, thoracic and mediastinal disorders Chest Pain	1.0% 2/200 • Number of events 2 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Infections and infestations Influenza	1.0% 2/200 • Number of events 2 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Gastrointestinal disorders Gastrointestinal hemorhage	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Endocrine disorders Protein-losing gastroenteropathy	0.50% 1/200 • Number of events 2 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Paralysis	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Vascular disorders Arrthythema	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Gastrointestinal disorders Intestinal obstruction	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Reproductive system and breast disorders Menorrhagia	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Renal and urinary disorders Renal Failure	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Psychiatric disorders Bipolar I disorder	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Cardiac disorders Intracardiac Thrombus	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Gastrointestinal disorders Anal hemorrhage	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Gastrointestinal disorders Constipation	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Migraine	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Cardiac disorders Cardiac Failure	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Gastrointestinal disorders Appendicitis	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Vascular disorders Cerebral Vascular Accident	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Nervous system disorders Fatigue	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infections	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.
Psychiatric disorders Depression	0.00% 0/200 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.	0.50% 1/200 • Number of events 1 • Adverse Events were recorded over the 26 weeks of study period plus an additional 3 months of follow-up.