Skip to Main content Skip to Navigation
Journal articles

Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial.

Sophie Leducq 1, 2, * Agnès Caille 1 Sébastien Barbarot 3 Nathalie Beneton 4 Didier Bessis 5 Olivia Boccara 6 Anne-Claire Bursztejn 7 Christine Chiaverini 8 Anne Dompmartin 9 Catherine Droitcourt 10 Valérie Gissot 1 Dominique Goga 2 Laurent Guibaud 11 Denis Herbreteau 2 Anne Le Touze 2 Christine Léauté-Labrèze 12 Gérard Lorette 2 Stephanie Mallet 13 Ludovic Martin 14 Juliette Mazereeuw-Hautier 15 Alice Phan 16 Patrice Plantin 17 Isabelle Quéré 17 Pierre Vabres 18 Helene Bourgoin 18 Bruno Giraudeau 1 Annabel Maruani 1, 2 . Groupe de Recherche de la Société Française de Dermatologie Pédiatrique
Abstract : Abstract Background: Cutaneous microcystic lymphatic malformations (CMLMs) are rare conditions in children and adults. They present as clusters of vesicles full of lymph and blood to various extents, inducing maceration, esthetic impairment, pain, and impaired quality of life. The treatment is challenging. Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Topical sirolimus has recently been reported as effective in a few reports of patients with CMLMs. The objective is to compare the efficacy and safety of a 12-week application of 0.1% topical sirolimus versus topical vehicle in CMLMs in children and adults. Methods: This French blinded multicenter within-person randomized controlled phase 2 trial aims to include 55 patients aged ≥ 6 years who have a primary CMLM. The CMLM will be divided into two equal areas that will be randomly allocated to 0.1% topical sirolimus or topical vehicle applied for 12 weeks. At the end of the 12-week period, the patient/ parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for eight more weeks. Patients will be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy. The primary outcome will be improvement of the CMLM in the area treated with topical sirolimus compared to the area treated with topical vehicle by the investigator physician (blinded to the treatment) with the Physician Global Assessment score at week 12. Secondary outcomes will include: assessment of efficacy by independent experts on the basis of standardized photographs; impact on quality of life; efficacy for oozing, bleeding, erythema, and thickness evaluated by the investigators; and global efficacy as well as efficacy for functional and aesthetic impairment evaluated by the patient. Systemic passage of sirolimus will be measured at weeks 6, 12, and 20, and at week 16 for CMLMs ≥ 900 cm2. For patients with CMLMs, topical sirolimus could be a non-invasive and well-tolerated therapeutic option. If the trial demonstrates efficacy and safety of this treatment, this result will lead to a real change in the management of this condition, and 0.1% sirolimus cream would become the first-line treatment. Discussion: For patients with CMLMs, topical sirolimus could be a non-invasive and well-tolerated therapeutic option. If the trial demonstrates efficacy and safety of this treatment, this result will lead to a real change in the management of this condition, and 0.1% sirolimus cream would become the first-line treatment. .
Complete list of metadata

Cited literature [37 references]  Display  Hide  Download

https://hal.inrae.fr/hal-02622848
Contributor : Migration Prodinra <>
Submitted on : Tuesday, May 26, 2020 - 6:47:09 AM
Last modification on : Tuesday, March 30, 2021 - 11:26:02 AM

File

2019_Leducq_Trials_1.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Sophie Leducq, Agnès Caille, Sébastien Barbarot, Nathalie Beneton, Didier Bessis, et al.. Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial.. Trials, BioMed Central, 2019, 20 (1), ⟨10.1186/s13063-019-3767-8⟩. ⟨hal-02622848⟩

Share

Metrics

Record views

114

Files downloads

209