Trial Outcomes & Findings for Sildenafil for the Treatment of Lymphatic Malformations (NCT NCT02335242)
NCT ID: NCT02335242
Last Updated: 2022-11-17
Results Overview
Participants will be followed for the duration of the study, an expected average of 20 weeks.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
22 participants
Primary outcome timeframe
Baseline, week 20
Results posted on
2022-11-17
Participant Flow
78 individuals were assessed for eligibility; 22 were enrolled, and 19 were randomized to a study arm.
Participant milestones
| Measure |
Double-Blind Placebo Then Open-Label Sildenafil
Placebo (resembling Revatio) for 20 weeks. Participants randomized to placebo had the option to enter a 20-week open-label phase to receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.
|
Double-Blind Sildenafil
Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.
|
|---|---|---|
|
Randomized Phase (20 Weeks)
STARTED
|
8
|
11
|
|
Randomized Phase (20 Weeks)
COMPLETED
|
7
|
11
|
|
Randomized Phase (20 Weeks)
NOT COMPLETED
|
1
|
0
|
|
Open-label Phase (20 Weeks)
STARTED
|
6
|
0
|
|
Open-label Phase (20 Weeks)
COMPLETED
|
6
|
0
|
|
Open-label Phase (20 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Follow-up Period (12 Weeks)
STARTED
|
6
|
11
|
|
Follow-up Period (12 Weeks)
COMPLETED
|
4
|
10
|
|
Follow-up Period (12 Weeks)
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Double-Blind Placebo Then Open-Label Sildenafil
Placebo (resembling Revatio) for 20 weeks. Participants randomized to placebo had the option to enter a 20-week open-label phase to receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.
|
Double-Blind Sildenafil
Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.
|
|---|---|---|
|
Randomized Phase (20 Weeks)
Withdrawal by Subject
|
1
|
0
|
|
Follow-up Period (12 Weeks)
Lost to Follow-up
|
1
|
0
|
|
Follow-up Period (12 Weeks)
Discontinued intervention
|
1
|
1
|
Baseline Characteristics
Ethnicity data are available for only 6 participants in the placebo group.
Baseline characteristics by cohort
| Measure |
Double-Blind Placebo Then Open-Label Sildenafil
n=8 Participants
Placebo (resembling Revatio) for 20 weeks. Participants randomized to placebo had the option to enter a 20-week open-label phase to receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.
|
Double-Blind Sildenafil
n=11 Participants
Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
8 Participants
n=8 Participants
|
11 Participants
n=11 Participants
|
19 Participants
n=19 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=8 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=19 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=8 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=19 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=8 Participants
|
6 Participants
n=11 Participants
|
9 Participants
n=19 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=8 Participants
|
5 Participants
n=11 Participants
|
10 Participants
n=19 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=6 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
5 Participants
n=11 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
6 Participants
n=17 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=6 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
6 Participants
n=11 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
11 Participants
n=17 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=6 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
0 Participants
n=11 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
0 Participants
n=17 Participants • Ethnicity data are available for only 6 participants in the placebo group.
|
|
Race/Ethnicity, Customized
African American
|
1 Participants
n=6 Participants • Race data are available for only 6 participants in the placebo group.
|
0 Participants
n=11 Participants • Race data are available for only 6 participants in the placebo group.
|
1 Participants
n=17 Participants • Race data are available for only 6 participants in the placebo group.
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=6 Participants • Race data are available for only 6 participants in the placebo group.
|
2 Participants
n=11 Participants • Race data are available for only 6 participants in the placebo group.
|
2 Participants
n=17 Participants • Race data are available for only 6 participants in the placebo group.
|
|
Race/Ethnicity, Customized
Indian
|
1 Participants
n=6 Participants • Race data are available for only 6 participants in the placebo group.
|
0 Participants
n=11 Participants • Race data are available for only 6 participants in the placebo group.
|
1 Participants
n=17 Participants • Race data are available for only 6 participants in the placebo group.
|
|
Race/Ethnicity, Customized
White
|
2 Participants
n=6 Participants • Race data are available for only 6 participants in the placebo group.
|
3 Participants
n=11 Participants • Race data are available for only 6 participants in the placebo group.
|
5 Participants
n=17 Participants • Race data are available for only 6 participants in the placebo group.
|
|
Race/Ethnicity, Customized
More than one race
|
1 Participants
n=6 Participants • Race data are available for only 6 participants in the placebo group.
|
1 Participants
n=11 Participants • Race data are available for only 6 participants in the placebo group.
|
2 Participants
n=17 Participants • Race data are available for only 6 participants in the placebo group.
|
|
Race/Ethnicity, Customized
Unknown/Not reported
|
1 Participants
n=6 Participants • Race data are available for only 6 participants in the placebo group.
|
5 Participants
n=11 Participants • Race data are available for only 6 participants in the placebo group.
|
6 Participants
n=17 Participants • Race data are available for only 6 participants in the placebo group.
|
|
Region of Enrollment
United States
|
8 Participants
n=8 Participants
|
11 Participants
n=11 Participants
|
19 Participants
n=19 Participants
|
|
Lesion volume
|
49 mm^3
n=6 Participants • Baseline lesion volume data are available for only 6 participants in the placebo group.
|
144 mm^3
n=11 Participants • Baseline lesion volume data are available for only 6 participants in the placebo group.
|
87 mm^3
n=17 Participants • Baseline lesion volume data are available for only 6 participants in the placebo group.
|
PRIMARY outcome
Timeframe: Baseline, week 20Population: Participants who completed each treatment period are included in the analysis
Participants will be followed for the duration of the study, an expected average of 20 weeks.
Outcome measures
| Measure |
Double-Blind Placebo
n=7 Participants
Placebo (resembling Revatio) for 20 weeks, followed by a 12 week follow-up period.
|
Open-Label Sildenafil
n=6 Participants
Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.
|
Double-blind Sildenafil
n=10 Participants
Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.
|
|---|---|---|---|
|
Change in Lesion Volume of the Test Medication as Evaluated by MRI Examination.
|
5.89 percentage of volume
Standard Deviation 13.5
|
-8.54 percentage of volume
Standard Deviation 12.1
|
-0.642 percentage of volume
Standard Deviation 18.3
|
SECONDARY outcome
Timeframe: Baseline, week 20Population: Participants with data at both baseline and week 20 are included in the analysis
Subject's evaluation of the overall change in lymphatic malformation. Participants will be followed from baseline to 20 weeks. Patients rated change as no improvement, minimal improvement (1-25% change), fair improvement (25-50% change), good improvement (50-75% change), and excellent improvement (75-100% change).
Outcome measures
| Measure |
Double-Blind Placebo
n=5 Participants
Placebo (resembling Revatio) for 20 weeks, followed by a 12 week follow-up period.
|
Open-Label Sildenafil
n=8 Participants
Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.
|
Double-blind Sildenafil
Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.
|
|---|---|---|---|
|
Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score
No improvement
|
1 Participants
|
2 Participants
|
—
|
|
Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score
Minimal improvement
|
2 Participants
|
4 Participants
|
—
|
|
Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score
Fair improvement
|
0 Participants
|
1 Participants
|
—
|
|
Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score
Good improvement
|
2 Participants
|
1 Participants
|
—
|
|
Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score
Excellent improvement
|
0 Participants
|
0 Participants
|
—
|
Adverse Events
Double-Blind Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Open-Label Sildenafil
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Double-Blind Sildenafil
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Double-Blind Placebo
n=8 participants at risk
Placebo (resembling Revatio) for 20 weeks.
|
Open-Label Sildenafil
n=6 participants at risk
Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg).
|
Double-Blind Sildenafil
n=10 participants at risk
Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg).
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cold
|
87.5%
7/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
33.3%
2/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
60.0%
6/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
1/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
33.3%
2/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
30.0%
3/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
12.5%
1/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
33.3%
2/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
10.0%
1/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Gastrointestinal disorders
Abdominal pain/bloating
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
16.7%
1/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
20.0%
2/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Gastrointestinal disorders
Nausea/vomit
|
25.0%
2/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
16.7%
1/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
40.0%
4/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Gastrointestinal disorders
Loose stool/increase bowel movement
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
16.7%
1/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
30.0%
3/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
0.00%
0/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
10.0%
1/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Gastrointestinal disorders
Acute gastroenteritis/viral gastroenteritis
|
12.5%
1/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
0.00%
0/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
10.0%
1/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Nervous system disorders
Headaches
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
33.3%
2/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
50.0%
5/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
General disorders
Fever
|
62.5%
5/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
0.00%
0/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
10.0%
1/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Vascular disorders
Intermittent flushing
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
16.7%
1/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
10.0%
1/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Infections and infestations
Cellulitis
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
16.7%
1/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
0.00%
0/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/8 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
16.7%
1/6 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
0.00%
0/10 • Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place