suPERficial Slow-flow Vascular malFORMations Treated With sirolimUS
Status:
Completed
Trial end date:
2019-03-01
Target enrollment:
Participant gender:
Summary
The most recent classification, adopted by International Society for the Study of Vascular
Anomalies (ISSVA) in 1996, and updated in Melbourne in 2014, divides these lesions into two
broad categories: vascular tumors and vascular malformations. Vascular malformations (VMs)
are subdivided into high-flow VM and slow-flow VM.
Slow-flow VMs consist of congenital anomalies which may involve abnormal capillaries vessels,
venous vessels, lymphatic vessels or combination of several of them. They can be superficial
(involving cutaneous and subcutaneous tissues) and/or may have visceral involvement. They can
be limited or diffuse, and are sometimes components of genetic hypertrophic syndromes.
The diagnosis of slow-flow VMs is performed on physical examination (biopsy may be required
for confirmation), and is completed with imaging (ultrasonography and magnetic resonance
imaging (MRI)). Slow-flow VMs may be particularly voluminous; associated with underlying
hypertrophy responsible for functional impairment; painful; associated with seepage or
continuous cutaneous bleeding; complicated with visceral signs or hematologic disturbances
(anemia, thrombopenia). Management requires dedicated multispecialty care. There are no
guidelines for treatment, and management may include no intervention - but natural history of
these VMs is progressive worsening -, compression by physical bandage, sclerotherapy,
resection (when feasible),anti-inflammatory or anti-coagulation drugs.
Case reports and series have provided evidence for supporting the need for a clinical trial
of sirolimus by reporting successful treatment on several children with complicated vascular
anomalies. The choice of sirolimus is rational. Mammalian target of rapamycin (mTOR) is a
serine/threonine kinase regulated by phosphoinositide-3-kinase involved in cell mobility,
cell growth and angiogenesis. Sirolimus inhibits mTOR, which induces inhibition of
angiogenesis, in particular lymphangiogenesis, which has been demonstrated in several models.