Trial Outcomes & Findings for Evaluation of Fontan-associated Hepatic Stiffness and the Efficacy of Udenafil in Reducing Liver Stiffness (NCT NCT03430583)
NCT ID: NCT03430583
Last Updated: 2025-10-14
Results Overview
Liver stiffness was measured at baseline and 52 weeks using Ultrasound Shear Wave Elastography (USWE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
88 participants
Primary outcome timeframe
52 weeks
Results posted on
2025-10-14
Participant Flow
Participant milestones
| Measure |
Udenafil Continuation (U+)
Treatment subgroup previously exposed to Udenafil
|
Udenafil Naive (U-)
Treatment subgroup naive to Udenafil
|
|---|---|---|
|
Overall Study
STARTED
|
36
|
52
|
|
Overall Study
COMPLETED
|
33
|
45
|
|
Overall Study
NOT COMPLETED
|
3
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
Baseline characteristics by cohort
| Measure |
Udenafil Continuation (U+)
n=36 Participants
Subset of subjects on Open-label extension study with Udenafil 87.5 mg BID treatment for 52 weeks, who received active Udenafil 87.5 mg BID treatment in FUEL study prior to enrolling to this study (FALD).
|
Udenafil Naive (-)
n=52 Participants
Subset of subjects on Open-label extension study with Udenafil 87.5 mg BID treatment for 52 weeks, who received Placebo BID treatment in FUEL study prior to enrolling to this study (FALD).
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
|
15.80 years
STANDARD_DEVIATION 1.992 • n=36 Participants
|
15.16 years
STANDARD_DEVIATION 1.961 • n=52 Participants
|
15.4 years
STANDARD_DEVIATION 2.0 • n=88 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=36 Participants
|
19 Participants
n=52 Participants
|
32 Participants
n=88 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=36 Participants
|
33 Participants
n=52 Participants
|
56 Participants
n=88 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=36 Participants
|
3 Participants
n=52 Participants
|
6 Participants
n=88 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=36 Participants
|
48 Participants
n=52 Participants
|
80 Participants
n=88 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=36 Participants
|
1 Participants
n=52 Participants
|
2 Participants
n=88 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=36 Participants
|
1 Participants
n=52 Participants
|
1 Participants
n=88 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=36 Participants
|
2 Participants
n=52 Participants
|
4 Participants
n=88 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=36 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=88 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=36 Participants
|
4 Participants
n=52 Participants
|
6 Participants
n=88 Participants
|
|
Race (NIH/OMB)
White
|
32 Participants
n=36 Participants
|
43 Participants
n=52 Participants
|
75 Participants
n=88 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=36 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=88 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=36 Participants
|
2 Participants
n=52 Participants
|
2 Participants
n=88 Participants
|
|
Body Mass Index (BMI)
|
21.9 kilograms per meter squared
STANDARD_DEVIATION 4.552 • n=36 Participants
|
21.4 kilograms per meter squared
STANDARD_DEVIATION 4.174 • n=52 Participants
|
21.6 kilograms per meter squared
STANDARD_DEVIATION 4.314 • n=88 Participants
|
|
Height
|
162.08 cm
STANDARD_DEVIATION 10.277 • n=36 Participants
|
164.89 cm
STANDARD_DEVIATION 8.936 • n=52 Participants
|
163.74 cm
STANDARD_DEVIATION 9.552 • n=88 Participants
|
|
Weight
|
57.48 Kg
STANDARD_DEVIATION 13.078 • n=36 Participants
|
58.42 Kg
STANDARD_DEVIATION 13.238 • n=52 Participants
|
58.03 Kg
STANDARD_DEVIATION 13.105 • n=88 Participants
|
|
Liver Stiffness by Ultrasound Shear Wave Elastography (USWE)
|
1.91 meters/sec
STANDARD_DEVIATION 0.380 • n=33 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
2.02 meters/sec
STANDARD_DEVIATION 0.450 • n=42 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
1.97 meters/sec
STANDARD_DEVIATION 0.422 • n=75 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
|
Liver Stiffness by Magnetic Resonance Elastography (MRE)
|
5.26 KiloPascal (kPa)
STANDARD_DEVIATION 0.927 • n=21 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
5.26 KiloPascal (kPa)
STANDARD_DEVIATION 1.453 • n=17 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
5.26 KiloPascal (kPa)
STANDARD_DEVIATION 1.173 • n=38 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
|
Enhanced Liver Fibrosis (ELF)
|
10.58 score on a scale
STANDARD_DEVIATION 0.915 • n=32 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
10.45 score on a scale
STANDARD_DEVIATION 0.853 • n=42 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
10.50 score on a scale
STANDARD_DEVIATION 0.877 • n=74 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
|
Brain Natriuretic Peptide (BNP)
|
16.89 pg/ml
STANDARD_DEVIATION 13.726 • n=32 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
17.20 pg/ml
STANDARD_DEVIATION 13.428 • n=44 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
17.07 pg/ml
STANDARD_DEVIATION 13.464 • n=76 Participants • Baseline results presented for subjects who have data at 52 weeks (i.e., paired-data points).
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Only participants with paired data points were included in the analysis population.
Liver stiffness was measured at baseline and 52 weeks using Ultrasound Shear Wave Elastography (USWE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.
Outcome measures
| Measure |
Udenafil Continuation (U+)
n=33 Participants
Treatment subgroup previously exposed to Udenafil
|
Udenafil Naive (U-)
n=42 Participants
Treatment subgroup naive to Udenafil
|
Total Udenafil
n=75 Participants
Total number of subjects exposed to Udenafil treatment during this open-label extension study.
|
|---|---|---|---|
|
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography
Baseline
|
1.91 meters per second
Standard Deviation 0.380
|
2.02 meters per second
Standard Deviation 0.450
|
1.97 meters per second
Standard Deviation 0.422
|
|
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography
Week 52
|
1.86 meters per second
Standard Deviation 0.288
|
1.96 meters per second
Standard Deviation 0.349
|
1.92 meters per second
Standard Deviation 0.325
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Only participants with paired data points were included in the analysis population.
Liver stiffness was measured at baseline and 52 weeks using Magnetic Resonance Elastography (MRE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.
Outcome measures
| Measure |
Udenafil Continuation (U+)
n=21 Participants
Treatment subgroup previously exposed to Udenafil
|
Udenafil Naive (U-)
n=17 Participants
Treatment subgroup naive to Udenafil
|
Total Udenafil
n=38 Participants
Total number of subjects exposed to Udenafil treatment during this open-label extension study.
|
|---|---|---|---|
|
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Magnetic Resonance Elastography
Baseline
|
5.26 kiloPascal (kPa)
Standard Deviation 0.927
|
5.26 kiloPascal (kPa)
Standard Deviation 1.453
|
5.26 kiloPascal (kPa)
Standard Deviation 1.173
|
|
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Magnetic Resonance Elastography
Week 52
|
4.95 kiloPascal (kPa)
Standard Deviation 1.080
|
5.50 kiloPascal (kPa)
Standard Deviation 1.550
|
5.20 kiloPascal (kPa)
Standard Deviation 1.322
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Only participants with paired data points were included in the analysis population.
Overall ELF score. ELF score is based on the serum levels of hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1), and calculated using the following formula: ELF score= 2.494+0.846 In(CHA)+0.391 In(CPIIINP)+0.391 In(CTIMP-1). The levels of each component were as assessed individually and as part of the calculated ELF score as continuous variables. The normal range in healthy subjects ≤20 years of age is 6.9 - 8.8. Correlations between ELF and the degree of liver fibrosis have not been established in patients with Fontan circulation, however, a decrease in ELF score is associated with improved liver health in other disease states.
Outcome measures
| Measure |
Udenafil Continuation (U+)
n=32 Participants
Treatment subgroup previously exposed to Udenafil
|
Udenafil Naive (U-)
n=42 Participants
Treatment subgroup naive to Udenafil
|
Total Udenafil
n=74 Participants
Total number of subjects exposed to Udenafil treatment during this open-label extension study.
|
|---|---|---|---|
|
Effect of Udenafil 87.5 mg BID on Enhanced Liver Fibrosis (ELF) Score After 52 Weeks of Treatment
Baseline
|
10.58 score on a scale
Standard Deviation 0.915
|
10.45 score on a scale
Standard Deviation 0.853
|
10.50 score on a scale
Standard Deviation 0.877
|
|
Effect of Udenafil 87.5 mg BID on Enhanced Liver Fibrosis (ELF) Score After 52 Weeks of Treatment
Week 52
|
9.72 score on a scale
Standard Deviation 0.818
|
9.79 score on a scale
Standard Deviation 0.750
|
9.76 score on a scale
Standard Deviation 0.776
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Only participants with paired data points were included in the analysis population.
Brain Natriuretic Peptide (BNP) was measured at baseline and 52 weeks of treatment. BNP is a biomarker of overall cardiac function across a variety of disease states. A decrease in value is associated with improved cardiac function.
Outcome measures
| Measure |
Udenafil Continuation (U+)
n=32 Participants
Treatment subgroup previously exposed to Udenafil
|
Udenafil Naive (U-)
n=44 Participants
Treatment subgroup naive to Udenafil
|
Total Udenafil
n=76 Participants
Total number of subjects exposed to Udenafil treatment during this open-label extension study.
|
|---|---|---|---|
|
Effect of Udenafil 87.5 mg BID on Brain Natriuretic Peptide After 52 Weeks of Treatment
Baseline
|
16.89 pg/ml
Standard Deviation 13.726
|
17.20 pg/ml
Standard Deviation 13.428
|
17.07 pg/ml
Standard Deviation 13.464
|
|
Effect of Udenafil 87.5 mg BID on Brain Natriuretic Peptide After 52 Weeks of Treatment
Week 52
|
20.31 pg/ml
Standard Deviation 18.336
|
20.78 pg/ml
Standard Deviation 19.165
|
20.59 pg/ml
Standard Deviation 18.698
|
Adverse Events
Udenafil 87.5 mg BID
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place