Sirolimus for severe arteriovenous malformations

Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations

This trial will see if taking oral sirolimus can shrink superficial arteriovenous malformations and reduce symptoms in people aged 2 and older.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire, Amiens (Academic / other)
• Locations: 13 sites (Brussels and 12 other locations)
• Trial ID: NCT02042326 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study gives oral sirolimus to children (age ≥2), adolescents, and adults with superficial arteriovenous malformations to measure changes in lesion volume and symptoms. The rationale is that sirolimus inhibits mTOR and has anti-proliferative and anti-angiogenic effects that may slow or reverse abnormal vessel growth. Patients are screened for contraindications (including immunosuppression, active chronic infections, pregnancy, and relevant allergies) and must agree to contraception if of childbearing potential. Safety monitoring is included to track adverse effects and treatment response over the study period.

Who should consider this trial

Good fit: People aged 2 years and older with superficial arteriovenous malformations classified as Schöbinger stage II–IV who can take oral medication and comply with study visits and contraception requirements.

Not a fit: Patients who are pregnant or breastfeeding, have significant immunosuppression or chronic active infections (hepatitis B/C, HIV), prior organ transplant, known allergy to macrolides or peanut/soy, or children under 2 are not appropriate for this treatment and unlikely to benefit in this protocol.

Why it matters

Potential benefit: If successful, sirolimus could reduce AVM size and symptoms such as pain or bleeding, potentially avoiding or delaying more invasive procedures.

How similar studies have performed: Small case series and reports have shown promising responses to sirolimus for various vascular anomalies including some AVMs, but large randomized data are limited.

Eligibility criteria

Inclusion Criteria:

* Patients (adults, adolescents and children older than 2 years), with arteriovenous malformation stage II + III or IV (according to Schöbinger's classification) : active or quiescent, marked or not by hemorrhagic phenomena.
* Patients (parents for minors) must sign a consent form established after clear information risks and expected benefits of the study.
* Patients (major and minor of childbearing age) must have effective contraception during the study period and continuing until 12 weeks after the end of treatment
* Negative pregnancy blood test for women of childbearing age.

Exclusion Criteria:

* Chronic or acquired immunosuppression :

  * patients with transplanted organ or who received a hematopoietic stem cell
  * patient with congenital immunodeficiency
* Patients implanted with chronic active infection associated with hepatitis B , hepatitis C or HIV
* Pregnant or nursing woman.
* Allergy to macrolides
* Allergy to peanut or soya
* Hypersensitivity to " Sirolimus " or any of the excipients of the investigational product
* Contraindications to performing an MRI
* Leukopenia below 1 000 /mm3
* Thrombocytopenia lower to 80,000 /mm3
* Anemia with Hb \< 9 g/dl
* Elevated transaminase \> 2.5 N
* History of cancer less than two years before the inclusion
* Surgery older than 2 months before inclusion
* Active infection (viral and bacterial ) on the date of inclusion
* Hypercholesterolemia \> 7 mmol / l despite appropriate medical treatment
* Hyperlipidemia \> 2 mmol / l despite appropriate medical treatment
* Uncontrolled diabetes
* Patients unable to follow a clinical study
* Major under guardianship, persons deprived of their liberty

Where this trial is running

Brussels and 12 other locations

• Ucl — Brussels, Belgium (Not_yet_recruiting)
• CHU Amiens — Amiens, France (Recruiting)
• CHU Bordeaux — Bordeaux, France (Not_yet_recruiting)
• CHU Dijon — Dijon, France (Recruiting)
• CHRU Lille — Lille, France (Not_yet_recruiting)
• HCL Lyon — Lyon, France (Recruiting)
• Aphm — Marseille, France (Not_yet_recruiting)
• CHU Montpellier — Montpellier, France (Not_yet_recruiting)
• CHU Nancy — Nancy, France (Not_yet_recruiting)
• CHU Nice — Nice, France (Not_yet_recruiting)
• Aphp — Paris, France (Not_yet_recruiting)
• CHU Strasbourg — Strasbourg, France (Not_yet_recruiting)
• CHU Tours — Tours, France (Not_yet_recruiting)

Study contacts

• Study coordinator: Bernard DEVAUCHELLE, MD, PhD

Conditions Arteriovenous Malformations; Sirolimus; Maxillofacial Surgery