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 |
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Recruitment Status :
Recruiting
First Posted : January 22, 2014
Last Update Posted : February 8, 2023
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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 |
| 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 |
| Arm | Intervention/treatment |
|---|---|
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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 |
- 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).
- 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
- 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.
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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:
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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
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
| Contact: Bernard DEVAUCHELLE, MD, PhD | +33322668325 | devauchelle.bernard@chu-amiens.fr | |
| Contact: Sylvie TESTELIN, MD, PhD | testelin.sylvie@chu-amiens.fr |
| Belgium | |
| UCL | Not yet recruiting |
| Bruxelles, Belgium | |
| France | |
| 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 | |
| Study Director: | Bernard DEVAUCHELLE, MD, PhD | CHU Amiens | |
| Study Chair: | Emmanuel MORELON, MD, PhD | HCL Lyon |
| 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 |
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Arteriovenous Malformations Sirolimus Maxillofacial Surgery |
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Hemangioma Arteriovenous Malformations Congenital Abnormalities Vascular Malformations Cardiovascular Abnormalities Cardiovascular Diseases Vascular Diseases Neoplasms, Vascular Tissue Neoplasms by Histologic Type Neoplasms |
Sirolimus Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |