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

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ClinicalTrials.gov Identifier: NCT02042326
Recruitment Status : Recruiting
First Posted : January 22, 2014
Last Update Posted : February 8, 2023
Information provided by (Responsible Party):
Centre Hospitalier Universitaire, Amiens

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.

Condition or disease Intervention/treatment Phase
Arteriovenous Malformations Drug: Sirolimus Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations
Actual Study Start Date : September 12, 2014
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Drug: Sirolimus
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

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. Treatment efficacy at M3 [ Time Frame: After 3 months of treatment ]
  2. Treatment efficacy at M6 [ Time Frame: After 6 months of treatment ]
  3. Treatment efficacy at M9 [ Time Frame: After 9 months of treatment ]
  4. Treatment tolerability [ Time Frame: One year ]
    Number and description of serious advent events

  5. Treatment Impact on 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02042326

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Contact: Bernard DEVAUCHELLE, MD, PhD +33322668325 devauchelle.bernard@chu-amiens.fr
Contact: Sylvie TESTELIN, MD, PhD testelin.sylvie@chu-amiens.fr

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UCL Not yet recruiting
Bruxelles, Belgium
CHU Amiens 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 Recruiting
Dijon, France, 21000
Contact: Pierre VABRES, MD PhD         
Principal Investigator: Pierre VABRES, MD PhD         
CHRU Lille Not yet recruiting
Lille, France, 59000
HCL Lyon Recruiting
Lyon, France, 69000
Contact: Pierre BRETON, MD PhD       pierre.breton@chu-lyon.fr   
Contact: Laurent GUIBAUD, MD PhD       laurent.guibaud@chu-lyon.fr   
Principal Investigator: Pierre BRETON         
Principal Investigator: Laurent GUIBAUD         
APHM Not yet recruiting
Marseille, France, 13000
Contact: Stéphanie MALLET, MD       stephanie.mallet@ap-hm.fr   
Principal Investigator: Jean-Michel BARTOLI         
Sub-Investigator: Stéphanie MALLET, MD         
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
Sponsors and Collaborators
Centre Hospitalier Universitaire, Amiens
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Study Director: Bernard DEVAUCHELLE, MD, PhD CHU Amiens
Study Chair: Emmanuel MORELON, MD, PhD HCL Lyon
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Responsible Party: Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier: NCT02042326    
Other Study ID Numbers: PHRCN10-PR-DEVAUCHELLE
2011-000321-69 ( EudraCT Number )
First Posted: January 22, 2014    Key Record Dates
Last Update Posted: February 8, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Centre Hospitalier Universitaire, Amiens:
Arteriovenous Malformations
Maxillofacial Surgery
Additional relevant MeSH terms:
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Arteriovenous Malformations
Congenital Abnormalities
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Vascular Diseases
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs