Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations (MAV-RAPA)
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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations|
- Treatment efficacy at M12 [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]
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).
- Treatment efficacy at M3 [ Time Frame: After 3 months of treatment ] [ Designated as safety issue: No ]
- Treatment efficacy at M6 [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
- Treatment efficacy at M9 [ Time Frame: After 9 months of treatment ] [ Designated as safety issue: No ]
- Treatment tolerability [ Time Frame: One year ] [ Designated as safety issue: Yes ]Number and description of serious advent events
- Quality of life [ Time Frame: Before treatment initiation and after 12 months of treatment ] [ Designated as safety issue: No ]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.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
Experimental: Sirolimus treatment
Patients will receive sirolimus (Rapamune). The dose should be adjusted to obtain a residual plasma rate of 8 to 12 ng/ml in 4 weeks. This serum level will be maintained throughout the duration of the study in the absence of side effects. In case of intolerance that do not justify the discontinuation of treatment, the dose may be reduced by maintaining a serum level greater than 3 ng/ml.
The starting dose will be 2 mg per day, and will be adapted every week for one month.
The preferred dosage form is tablet form. To prevent common side effects in early treatment, corticosteroids based prednisolone (SOLUPRED) will be established at a dose of 0.5 mg/ kg/day for the first week of treatment.
For patients with swallowing problems, and for children under 6 years and / or who have an inability to swallow tablets, the 1mg/ml solution form should be used.
Other Name: Rapamune
Please refer to this study by its ClinicalTrials.gov identifier: NCT02042326
|Contact: Bernard DEVAUCHELLE, MD, PhDfirstname.lastname@example.org|
|Contact: Sylvie TESTELIN, MD, PhDemail@example.com|
|UCL||Not yet recruiting|
|Amiens, France, 80000|
|Principal Investigator: Bernard DEVAUCHELLE, MD, PhD|
|Sub-Investigator: Sylvie TESTELIN, MD, PhD|
|CHU Bordeaux||Not yet recruiting|
|Bordeaux, France, 33000|
|CHU Dijon||Not yet recruiting|
|Dijon, France, 21000|
|CHRU Lille||Not yet recruiting|
|Lille, France, 59000|
|HCL Lyon||Not yet recruiting|
|Lyon, France, 69000|
|APHM||Not yet recruiting|
|Marseille, France, 13000|
|CHU Montpellier||Not yet recruiting|
|Montpellier, France, 34000|
|CHU Nancy||Not yet recruiting|
|Nancy, France, 54000|
|CHU Nice||Not yet recruiting|
|Nice, France, 06000|
|APHP||Not yet recruiting|
|Paris, France, 75000|
|CHU Strasbourg||Not yet recruiting|
|Strasbourg, France, 67000|
|CHU Tours||Not yet recruiting|
|Tours, France, 37000|
|Study Director:||Bernard DEVAUCHELLE, MD, PhD||CHU Amiens|
|Study Chair:||Emmanuel MORELON, MD, PhD||HCL Lyon|