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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary:

The aim of the study is to evaluate the efficacy and safety of sirolimus (oral form), to decrease the volume and symptoms due to superficial arteriovenous malformations (AVM).

Sirolimus has properties that reduce the activity of the immune system (immunosuppressant), to fight against the proliferation of cancer cells (anti- tumor) and also reduce the proliferation of blood vessels (anti -vascular). Sirolimus is primarily used in transplant patients to prevent organ transplant rejection. Many animal and laboratory studies were carried out and demonstrate in particular the activity of sirolimus on vessels. It is this anti- vascular effect that could help treat arteriovenous malformations.


Detailed Summary: Anti-proliferative and anti-angiogenic properties of Sirolimus (Rapamycin®) are the basis of the rationale to use it in the treatment of arteriovenous malformations, for which the pathophysiology remains poorly understood. The interest of this class of drug is that inhibition of mTOR (mammalian target of rapamycin) may also block growth and / or angiogenic factors (other than VEGF) involved in the development of AVM. More specifically anti-VEGF drugs does not have that potential.
Sponsor: Centre Hospitalier Universitaire, Amiens

Current Primary Outcome: Treatment efficacy at M12 [ Time Frame: After 12 months of treatment ]

The efficacy of treatment is a composite criteria based on:

  • The proportion of patients with no evolution of the AVM during the study period,
  • The proportion of patients with a reduction in tumor volume of the AVM at least 30% of CT Angiography (CTA) criteria during the first year of the study (comparison of the volume of the AVM a year versus pre-inclusion).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Treatment efficacy at M3 [ Time Frame: After 3 months of treatment ]
  • Treatment efficacy at M6 [ Time Frame: After 6 months of treatment ]
  • Treatment efficacy at M9 [ Time Frame: After 9 months of treatment ]
  • Treatment tolerability [ Time Frame: One year ]
    Number and description of serious advent events
  • Quality of life [ Time Frame: Before treatment initiation and after 12 months of treatment ]
    Quality of life will be assessed before and at the end of the first year of treatment using a questionnaire given to patients. There is no questionnaire specifically tailored to vascular malformations in the literature. Thus the investigators adapted a document based on an evaluation of the quality of life for survivors of burn injury.


Original Secondary Outcome: Same as current

Information By: Centre Hospitalier Universitaire, Amiens

Dates:
Date Received: January 20, 2014
Date Started: September 2014
Date Completion: June 2018
Last Updated: August 1, 2016
Last Verified: August 2016