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

Key Points: Question: Is eppikajutsuto, a traditional Japanese (Kampo) herbal medicine, associated with reduced lesion volume among children with lymphatic malformations (LMs)? FINDINGS: In this nonrandomized clinical trial of 19 children with LMs, 10 (53%) achieved a 20% or greater reduction in lesion volume at 6 months. No serious adverse events were reported. Meaning: These findings suggest that eppikajutsuto was associated with a reduction in lesion volume and was well tolerated in children with LMs. This nonrandomized clinical trial evaluates the association of eppikajutsuto, a traditional Japanese (Kampo) herbal medicine, with lesion size in pediatric patients with lymphatic malformations. 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