Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life
Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life
Congenital vascular anomalies are uncommon and belong to the group of rare diseases.These
 vascular malformations can cause serious complications including obstruction of vital organs
 and their function, recurrent infection and significantly reduced quality of life of persons
 affected.Treatment options range from conservative to surgical extirpation or intralesional
 embolisation/sclerosis. Unfortunately, this is often not enough. Many patients still have
 complaints like severe pain and invalidation due to the lymphatic or venous malformation
 making a normal functional life impossible. Recent case reports mention the positive effects
 of refractory patients with Sirolimus. Sirolimus, also known as rapamycin, is currently the
 only FDA-approved mammalian target of rapamycin (mTOR) inhibitor.
Congenital vascular anomalies are uncommon and belong to the group of rare diseases. In 1996,
 the International Society of the Study of Vascular Anomalies adopted a new classification,
 distinguishing vascular malformations from vascular tumors. This classification was revised
 in 2014 and newly identified genetic features were taken into account. Vascular malformations
 feature dysplastic malformed vessels and are a consequence of a defective development of the
 embryonic vascular system. Vascular malformations can involve lymphatic vessels, capillaries,
 veins and arteries or even combinations. These vascular malformations are present at birth
 and grow with the child. Treatment options range from conservative to surgical extirpation or
 intralesional embolisation/sclerosis. Unfortunately, this is often not enough. Many patients
 still have complaints like severe pain and invalidation due to the lymphatic or venous
 malformation making a normal functional life impossible. These vascular malformations can
 cause serious complications including obstruction of vital organs and their function,
 recurrent infection and significantly reduced quality of life of persons affected. As the
 natural course of the disease affects multiple body systems, the therapeutic management is
 challenging. To date, no other medical treatment options are available. Although standard
 pain medication is given according the (inter) national pain protocols, patients still suffer
 pain and are not able to function normally in daily life. Majority (60-70% percent of the
 patients) of the patients is not able to have a normal life, with a normal job and normal
 social activities. Children are often not able to go to school normally, cannot play outside
 and have pain at the site of the malformation. The vast majority of literature reporting
 medical therapies for vascular anomalies consists of case reports and small series and is
 complicated by publication bias (negative findings are often not published), inconsistent use
 of nomenclature, and the absence of clinical trials. Recent case reports mention the positive
 effects of refractory patients with Sirolimus. Sirolimus, also known as rapamycin, is
 currently the only FDA-approved mammalian target of rapamycin (mTOR) inhibitor, indicated for
 prevention of kidney allograft rejection in adults and children 13 years or older, but is
 commonly used to manage organ rejection in younger children.
Inclusion Criteria:

 -  Diagnosis of Congenital venous malformation, or lymphatic malformation or combined.

 -  Age older than 1 yr.

 -  Patients (or legal guardians for children) have to be able to sign the informed
 consent

 -  Patients are either refractory to standard care such as medical treatment (low
 molecular weight heparins, pain medication etc.), surgical resection and/or
 sclerotherapy/embolization (ineffective or accompanied by major complications) or
 there is no possibility for surgical intervention anymore. Only patients that have a
 normal clinical screening (no signs for infection, normal bone marrow function, normal
 liver and kidney function, normal glucose metabolism etc.) can be included.

 -  Patients included have no cardiac impairment

 -  Patients have no gastrointestinal impairment as Sirolimus is absorbed
 gastro-intestinal and normal function is needed

 -  No other underlying medical disorder like Down syndrome or other syndromes

 -  Women of reproductive age have to be informed that contraceptive methods are

 -  mandatory during the study time, pregnant women are excluded

 -  Karnofsky score > 50

 Exclusion Criteria:

 -  No written informed consent

 -  Known hypersensitivity to drugs or metabolites from similar classes as study
 treatment.

 -  Patient has other concurrent severe and /or uncontrolled medical condition that would,
 in the investigator's judgment, contraindicated participation in the clinical study
 (e.g. acute or chronic pancreatitis, liver cirrhosis, active chronic hepatitis,
 severely impaired lung function with a spirometry ≤ 50% of the normal predicted value
 and/or O2 saturation ≤ 88% at rest, etc.)

 -  Recent history of primary malignancy ≤ 5 years

 -  Impaired cardiac function or clinically significant cardiac diseases

 -  Immunocompromised patients, including known seropositivity for HIV

 -  Patient with any other concurrent severe and /or uncontrolled medical condition that
 would,in the investigator's judgment, contraindicated participation in the clinical
 study.

 -  Pregnant or lactating women

 -  Karnofsky score < 50