Evidence map›Paper›PMID 37937645›Full record

Trial reportJCI insight2023

Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations.

Emmanuel Seront, An Van Damme, Catherine Legrand, Annouk Bisdorff-Bresson, Philippe Orcel, Thomas Funck-Brentano, Marie-Antoinette Sevestre, Anne Dompmartin, Isabelle Quere, Pascal Brouillard and 7 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02638389 (Phase III Multicentric Study Evaluating the Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care), which is not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
18.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02638389 phase3recruitingnot on this map

Phase III Multicentric Study Evaluating the Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care

TypeinterventionalSponsorCliniques universitaires Saint-Luc- Université Catholique de LouvainRan2016 to 2030Enrolled250ConditionsVascular MalformationsArmsSirolimus
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

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  17. Oral sirolimus therapy for patients with complex low-flow vascular malformations.Journal of vascular surgery. Venous and lymphatic disorders · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 4 countries.

Emmanuel SerontCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
An Van DammeCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Catherine LegrandISBA/LIDAM, UCLouvain, Louvain-la-Neuve, Belgium.
Annouk Bisdorff-BressonNeuroradiology Department of Pr Houdart Lariboisière Hospital, Center of vascular anomalies clinic VASCERN VASCA European Reference Centre, Paris, France.
Philippe OrcelDepartment of Rheumatology - DMU Locomotion, AP-HP Nord - University of Paris and INSERM U1132 BIOSCAR, Paris, France, Paris, France.
Thomas Funck-BrentanoDepartment of Rheumatology - DMU Locomotion, AP-HP Nord - University of Paris and INSERM U1132 BIOSCAR, Paris, France, Paris, France.
Marie-Antoinette SevestreVascular Medicine Department, CHU Amiens-Picardie, Amiens, France.
Anne DompmartinDepartment of Dermatology, CHU Université Caen Normandie, Caen, France.
Isabelle QuereIDESP, Univeristy of Montpellier - INSERM, CHU Montpellier, CRMR FAVA-Multi, Montpellier, France.
Pascal BrouillardHuman Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium.
Nicole RevencuCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Martina De BortoliHuman Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium.
Frank HammerCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Philippe ClapuytCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Dana DumitriuCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Miikka VikkulaCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Laurence M BoonCenter for Vascular Anomalies, Cliniques universitaires Saint-Luc, University of Louvain, VASCERN VASCA European Reference Centre, Brussels, Belgium.
Cliniques Universitaires Saint-Luc · BEInserm · FRde Duve Institute · BEAlbert Schweitzer Hospital · GACentre Hospitalier Universitaire Amiens-Picardie · FRHôpital Lariboisière · FRNormandie Université · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUNDSlow-flow vascular malformations frequently harbor activating mutations in the PI3K/AKT/mTOR cascade. Phase II trials pinpointed sirolimus effectiveness as a drug therapy. Efficacy and safety of sirolimus thus need to be evaluated in large prospective phase III trials.METHODSThe Vascular Anomaly-Sirolimus-Europe (VASE) trial, initiated in 2016, is a large multicentric prospective phase III trial (EudraCT 2015-001703-32), which evaluates efficacy and safety of sirolimus for 2 years in pediatric and adult patients with symptomatic slow-flow vascular malformations. In this interim analysis, we studied all patients enrolled up to October 2021 who received sirolimus for 12 or more months or who prematurely stopped the treatment.RESULTSThirty-one pediatric and 101 adult patients were included in this analysis; 107 completed 12 or more months of sirolimus, including 61 who were treated for the whole 2-year period. Sirolimus resulted in a clinical improvement in 85% of patients. The efficacy appeared within the first month for the majority of them. Grade 3-4 adverse events were observed in 24 (18%) patients; all resolved after treatment interruption/arrest. Sirolimus increased feasibility of surgery or sclerotherapy in 20 (15%) patients initially deemed unsuitable for intervention. Among the 61 patients who completed the 2-year treatment, 33 (54%) reported a recurrence of symptoms after a median follow-up of 13 months after sirolimus arrest. While there was no difference in efficacy, clinical improvement was faster but subsided more rapidly in PIK3CA-mutated (n = 24) compared with TIE2-mutated (n = 19) patients.CONCLUSIONSirolimus has a high efficacy and good tolerance in treatment of slow-flow vascular malformations in children and adults.TRIAL REGISTRATIONClinicalTrials.gov NCT02638389 and EudraCT 2015-001703-32.FUNDINGThe Fonds de la Recherche Scientifique (FNRS grants T.0247.19, P.C005.22, T.0146.16, and P.C013.20), the Fund Generet managed by the King Baudouin Foundation (grant 2018-J1810250-211305), the Walloon Region through the FRFS-WELBIO strategic research programme (WELBIO-CR-2019C-06), the MSCA-ITN network V.A. Cure no. 814316, the Leducq Foundation Networks of Excellence Program grant "ReVAMP" (LFCR grant 21CVD03), the European Union's Horizon 2020 research and innovation programme under grant agreement no. 874708 (Theralymph), the Swiss National Science Foundation under the Sinergia project no. CRSII5_193694, and a Pierre M. fellowship.

Indexed as

SirolimusVascular MalformationsAdultChildEuropeHumansPhosphatidylinositol 3-KinasesProspective StudiesPhosphatidylinositol 3-KinasesSirolimusAngiogenesisClinical TrialsGenetic diseasesLymphomas

Identifiers

PMID37937645
PMCPMC10721262
OpenAlexW4388451543

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.