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Sildenafil for the Treatment of Lymphatic Malformations
Trial ID: NCT02335242
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
Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations
- Be legally authorized representative of subjects willing and able to give consent.
Assent obtained for subjects 7 - 10 years old.
- Be between the ages of 6 months - 10 years of age at the time of entry into the study.
- Be at the minimum weight of 8 kg at the time of enrollment.
- Be required to have the clinical diagnosis of lymphatic malformation that appears to
be over 3 cm in greatest diameter in order to be evaluated for entry. A review of a
previous MRI examination may help confirm the entry criteria on subjects selected to
come to Stanford for the MRI screening.
- Have the lymphatic malformation cause enough disability for the subject that requires
them to consider systemic therapy.
- For female subjects: must not be pregnant or breast-feeding.
- Have a parent or legally authorized representative willing and able to ensure subject
is present for all required study visits.
- Have a required MRI examination to confirm that the lymphatic malformation is present
and is greater than 3 cm in diameter in order for the subjects to receive medication,
which happens during the initial screening evaluation portion of the trial.
- Have no contraindications for the use of sildenafil.
- Have a normal eye examination.
- Have normal liver and kidney function.
- Have no contraindication to MRI examinations such as metal implants, etc.
- Not be a smoker.
A Subject with any of the following criteria is not eligible for inclusion in this study:
- Medically unstable health status that may interfere with his/her ability to complete
- Has one or more of the following medical conditions:
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 contraindicated in association
with sildenafil within 15 days of inclusion:
- Organic nitrates in any form, either regularly or intermittently -- Consistent
with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to
potentiate the hypotensive effects of nitrates.
- Ritonavir and other Potent CYP3A Inhibitors --- Concomitant use of REVATIO with
ritonavir and other potent CYP3A inhibitors is not recommended.
- Alpha-blockers --- co-administering alpha-blockers with REVATIO because of
additive blood pressure-lowering effects
- Requires concomitant use of potent cytochrome P450 3A4 inhibitors (such as
ketoconazole, itraconazole, erythromycin, saquinavir), or concomitant use of
ritonavir. Also excluded are concomitant use of organic nitrates, alpha-blockers,
amlodipine, or cimetidine.
- Cannot confirm that the lesion is a lymphatic malformation or the lymphatic
malformation is less than 3 cm in its greatest diameter during the MRI screening.
- Has had extensive prior surgery or sclerotherapy to treat LM such that scarring may
interfere with evaluation and treatment effect of sildenafil.
- Have had recurrent infection and significant scarring of the lesion secondary to
infection to such an extent that the that scarring may interfere with evaluation and
treatment effect of sildenafil
- Known to have an allergy to sildenafil.
- Has ulcerated or currently infected LMs.
- Has diagnosis of the soft tissue tumor as LM not clinically certain.
- Participating in another clinical study which may interfere.
- Has a history of priapism or is diagnosed with sickle cell anemia or any other
disorder which may predispose to priapism.
drug: Sildenafil 20 mg tablets
other: Placebo tablets (resembling Revatio)
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Elidia C Tafoya, MPH