Eppikajutsuto for Treatment of Lymphatic Malformations in Children: A Nonrandomized Clinical Trial.

IMPORTANCE

Lymphatic malformations (LMs) are congenital vascular anomalies with limited treatment options. Eppikajutsuto, a traditional Japanese (Kampo) herbal medicine, is commonly used to treat inflammatory conditions and has been reported to reduce lesion volume in patients with LMs; however, data on its effectiveness in pediatric patients are needed.

OBJECTIVE

To evaluate the association of eppikajutsuto with reduced LM lesion volume in pediatric patients with LMs.

DESIGN, SETTING, AND

PARTICIPANTS

This open-label nonrandomized clinical trial was conducted from April 14, 2021, to September 30, 2024, at multiple centers in Japan. Eligible participants were 18 years or younger with a confirmed diagnosis of LM by imaging. Data were analyzed from October 14, 2024, to March 4, 2025.

INTERVENTION: Participants received eppikajutsuto granules (0.6 g/kg/d to ≤7.5 g/d) orally for 6 months.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients achieving a 20% or greater reduction in lesion volume, measured with magnetic resonance imaging volumetry at baseline and 6 months. Secondary outcomes included a 50% or greater reduction in lesion volume, median shrinkage rate, improvement in quality of life, and safety.

RESULTS

A total of 19 patients (10 male [52.6%]; mean [SD] age, 24.1 [29.4] months) were enrolled. A total of 10 patients (52.6%; 90% CI, 32.0%-73.0%) achieved a 20% or greater reduction in lesion volume at 6 months. The median shrinkage rate was 22.9% (IQR, -142.3% to 96.0%). No serious adverse events occurred, and medication adherence of 70% or greater was observed in 17 of 19 patients (89.5%).

CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial of children with LMs, eppikajutsuto was associated with a reduction in lesion volume and was well tolerated. Further studies, including randomized clinical trials, are warranted to confirm these findings.

TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCTs041210007.