An Investigational Pilot Study to Evaluate Sildenafil for the Treatment of Lymphatic Malformations
1. Written informed consent(s) for study participation and (where applicable) the use of
the participant's images are obtained according to national regulations from the
participant's parent(s) or guardian(s) prior to performing any study procedures.
2. The participant is 6 months to 10 years of age at inclusion.
3. The participant weight is at least 8kg.
4. A diagnosis of LM or mixed venous lymphatic malformation involving the skin and
subcutaneous tissue and at least 3cm based on clinical and radiographic criteria.
5. LMs may benefit from systemic therapy based on clinical criteria.
6. Females must not be pregnant or breast-feeding.
7. If participant is a child, parent/guardian must be able to follow instructions and
must be willing and able to ensure that the subject is present for all required study
8. Subject has no contraindication for use of sildenafil.
9. LMs may involve any part of the body.
10. Subject will have normal results on screening tests (eye exam, blood tests).
11. Subject has no contraindication for MRI examinations, such as metal implants, etc.
12. Subject must not be a smoker.
1. The participant has a medically unstable health status that may interfere with
his/her ability to complete the study.
2. The participant presents with 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 factors for developing non-arteritic anterior ischemic
optic neuropathy (NAION) including low ocular cup to disc ratio, age over 10,
diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking.
(Participants with Down syndrome, Turner syndrome, and Noonan syndrome will be
considered on a case-by-case basis).
3. The participant has received at least one of the following medications
contraindicated in association with sildenafil within 15 days of inclusion:
Alprostadil, Azole antifungals, Clarithromycins, Conivaptan, Delavirdine,
Erythromycins, Fluvoxamine, Grapefruit, Imatinib, Nefazodone, Nitrates/sodium
thiosulfate, Non-selective and selective alpha blockers, Protease inhibitors,
Rufinamide, Tadalafil, Telithromycin, Vardenafil, Yohimbe, Yohimbine, Amifostine,
4. The participant requires concomitant use of potent cytochrome P450 3A4 inhibitors
(such as ketoconazole, itraconazole, erythromycin, saquinavir) or concomitant use of
5. The patient has had extensive prior surgery or sclerotherapy to treat LM such that
scarring may interfere with the treatment effect of sildenafil.
6. The participant has previously been administered treatment for LMs or surgical
procedures have been performed to remove the index LMs.
7. Participant is currently pregnant or considering becoming pregnant in the next 20
8. The participant is known to have an allergy to sildenafil.
9. Ulcerated or currently infected LMs with pain.
10. Diagnosis of the soft tissue tumor as LM is not clinically certain.
11. The participant is participating in another clinical study.
12. The participant has a history of priapism or is diagnosed with sickle cell anemia or
any other disorder which may predispose to priapism.
13. The investigator may declare any subject ineligible for a valid medical reason.