A Phase 2 interventional study of Sildenafil 20 mg tablets and Placebo tablets (resembling Revatio) in Lymphatic Malformations and Lymphatic Diseases, sponsored by Stanford University. Completed at 3 sites in United States. Open to participants aged 6 Months to 10 Years. Per ClinicalTrials.gov, last updated 2022-11-17.
Sponsored by Stanford University · Phase 2, Interventional, and Supportive care
A Phase 2 study to evaluate safety and efficacy of sildenafil taken orally to improve or resolve lymphatic malformations in children. Subjects may receive either placebo or treatment in an oral dosage with an open label extension for subjects who received placebo. The study treatment assignment will be randomized in a double blind fashion. MRI examination will evaluate change in lesion volume due to treatment. Other safety and efficacy measures will be taken through the 32-week study duration.
Funding Source - FDA OOPD
Lymphatic malformations (LMs) are localized areas of abnormal development of the lymphatic system that commonly occur in the head and neck of children. LMs are considered a rare or orphan disease which causes complications including pain, ulceration, secondary infection, infiltration of other organs, and death. Current therapies involve surgical excision or methods of chemical or physical destruction of portions of lesions. No therapies are uniformly effective and all have the risk of significant adverse events. We recently witnessed almost complete resolution of a LM lesion in a child who was treated with sildenafil oral therapy for pulmonary arterial hypertension. We have subsequently evaluated additional subjects who improved with sildenafil. The goal of this clinical research trial is to document the benefit or absence of benefit of sildenafil therapy for LMs and identify which type of patient will benefit from sildenafil. This study is a double-blind placebo-controlled trial which involves precise documentation of volume changes associated with therapy or placebo by using MRI segmentation techniques. We will also observe and document the clinical response to sildenafil or placebo using clinical evaluation scores and surveys. The results of the study should identify characteristics of LM lesions which may suggest a beneficial response to sildenafil therapy. Sildenafil has very low risk of side effects in the dosage used in this trial. Documentation of an effective response of LMs to sildenafil will accelerate the interest in, and the ability to understand, the mechanisms of LM formation and treatment.
42 studies on the registry are indexed under Lymphatic Abnormalities; 17 are open to participants now.
This study's enrollment of 22 is below the median of 46 across 28 interventional studies indexed under Lymphatic Abnormalities.
Browse Lymphatic Abnormalities studies →Stanford University is the lead sponsor of 2,168 studies on the registry; 431 are open to participants now.
Of its 267 completed or terminated interventional studies of FDA-regulated products, 207 (78%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Subjects must:
Exclusion Criteria:
A Subject with any of the following criteria is not eligible for inclusion in this study:
Hepatic impairment, severe renal impairment, lymphedema conditions such as Milroy disease, Meige lymphedema, Hennekam syndrome, Njolstad syndrome, Aagenaes syndrome, and Fabry disease, hypotension or at risk for hypotension, seizures or history of seizures, any significant cardiovascular risk factors and any condition which requires participants to use nitric oxide donors or nitrates in any form, underlying anatomic or vascular risk factor for developing non-arteritic anterior ischemic optic neuropathy (NAION) including low ocular cup to disc ratio, diabetes, hypertension, coronary artery disease, or hyperlipidemia Participants with Down syndrome, Turner syndrome and Noonan syndrome will be considered on a case-by-case basis.
Has received at least one of the following medications in association with sildenafil within 15 days of inclusion:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Placebo Drug: Placebo tablets (resembling Revatio)
Other: Placebo tablets (resembling Revatio)
Active Drug: Sildenafil tablets (Revatio)
Drug: Sildenafil 20 mg tablets
Change in Lesion Volume of the Test Medication as Evaluated by MRI Examination.
Participants will be followed for the duration of the study, an expected average of 20 weeks.
Time frame: Baseline, week 20
Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score
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).
Time frame: Baseline, week 20
| Milestone | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil |
|---|---|---|
| Started | 8 | 11 |
| Completed | 7 | 11 |
| Not completed | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Milestone | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil |
|---|---|---|
| Started | 6 | 0 |
| Completed | 6 | 0 |
| Not completed | 0 | 0 |
| Milestone | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil |
|---|---|---|
| Started | 6 | 11 |
| Completed | 4 | 10 |
| Not completed | 2 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Discontinued intervention | 1 | 1 |
Participants will be followed for the duration of the study, an expected average of 20 weeks.
| percentage of volume | Double-Blind Placebo | Open-Label Sildenafil | Double-blind Sildenafil |
|---|---|---|---|
| Change in Lesion Volume of the Test Medication as Evaluated by MRI Examination. | 5.89 ± 13.5 | -8.54 ± 12.1 | -0.642 ± 18.3 |
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).
| Participants | Double-Blind Placebo | Double-Blind Sildenafil |
|---|---|---|
| No improvement | 1 | 2 |
| Minimal improvement | 2 | 4 |
| Fair improvement | 0 | 1 |
| Good improvement | 2 | 1 |
| Excellent improvement | 0 | 0 |
Collected over Up to 52 weeks in the Placebo then Open-Label Sildenafil group, and up to 32 weeks in the Sildenafil group. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Double-Blind Placebo | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| Open-Label Sildenafil | 0/6 (0%) | 0/6 (0%) | 5/6 (83.3%) |
| Double-Blind Sildenafil | 0/10 (0%) | 0/10 (0%) | 10/10 (100%) |
| Event | Double-Blind Placebo | Open-Label Sildenafil | Double-Blind Sildenafil |
|---|---|---|---|
| ColdRespiratory, thoracic and mediastinal disorders | 7/8 | 2/6 | 6/10 |
| FeverGeneral disorders | 5/8 | 0/6 | 1/10 |
| HeadachesNervous system disorders | 0/8 | 2/6 | 5/10 |
| Nausea/vomitGastrointestinal disorders | 2/8 | 1/6 | 4/10 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/8 | 2/6 | 3/10 |
| RhinorrheaRespiratory, thoracic and mediastinal disorders | 1/8 | 2/6 | 1/10 |
| Loose stool/increase bowel movementGastrointestinal disorders | 0/8 | 1/6 | 3/10 |
| Abdominal pain/bloatingGastrointestinal disorders | 0/8 | 1/6 | 2/10 |
| Intermittent flushingVascular disorders | 0/8 | 1/6 | 1/10 |
| CellulitisInfections and infestations | 0/8 | 1/6 | 0/10 |
| Age, Categorical(Participants) | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil | Total |
|---|---|---|---|
| <=18 years | 8 | 11 | 19 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil | Total |
|---|---|---|---|
| Female | 3 | 6 | 9 |
| Male | 5 | 5 | 10 |
| Ethnicity (NIH/OMB)(Participants) | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 5 | 6 |
| Not Hispanic or Latino | 5 | 6 | 11 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil | Total |
|---|---|---|---|
| African American | 1 | 0 | 1 |
| Asian | 0 | 2 | 2 |
| Indian | 1 | 0 | 1 |
| White | 2 | 3 | 5 |
| More than one race | 1 | 1 | 2 |
| Unknown/Not reported | 1 | 5 | 6 |
| Region of Enrollment(Participants) | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil | Total |
|---|---|---|---|
| United States | 8 | 11 | 19 |
| Lesion volume(mm^3) | Double-Blind Placebo Then Open-Label Sildenafil | Double-Blind Sildenafil | Total |
|---|---|---|---|
| Median | 49 (10 to 280) | 144 (49 to 856) | 87 (10 to 856) |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — The IPD will only be shared de-identified to our study staff and human subjects approved subsites. These results will eventually be published, but will be completed around 2022.
This study is completed, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sildenafil