Efficacy of Kangfuxin solution irrigation for ulcerative non-puerperal mastitis: A randomized controlled trial using a 2×2 factorial design

Background Ulcerative non-puerperal mastitis (NPM) is characterized by delayed healing and high recurrence. Effective pharmacological options are limited. Objective This study aimed to evaluate the efficacy and safety of Kangfuxin Solution (KFX) irrigation and to examine whether pathological subtype influences treatment response. Methods A prospective single-center randomized controlled trial was conducted using a 2×2 factorial design. A total of 240 patients with ulcerative plasma cell mastitis (PCM) or granulomatous lobular mastitis (GLM) were randomly assigned to receive KFX irrigation or normal saline irrigation, in addition to standardized oral therapy. Primary outcomes were therapeutic response assessed by an ordinal scale at one year. Secondary outcomes included inflammatory mass size, pain scores, recurrence, intervention duration, and safety. Analyses were performed in both intention-to-treat and per-protocol populations. The study protocol received initial approval from the Institutional Ethics Committee (IEC) of The First Affiliated Hospital of Zhejiang Chinese Medical University on May 4, 2021 (Approval No.: 2021–KL–025–01), which was maintained through successive annual re-approvals obtained on July 22, 2021, and July 20, 2022, each valid for one year. This trial was retrospectively registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR) and received approval on January 17, 2026 (Registration number: ITMCTR2026000088; URL: https://itmctr.ccebtcm.org.cn/mgt/project/view/2012446768452730880 ). Results KFX irrigation significantly improved therapeutic efficacy versus saline control in both the per-protocol (OR=2.0, 95%CI: 1.2–3.3) and intention-to-treat (OR=1.9, 95%CI: 1.2–3.1) analyses, with a more pronounced benefit observed in PCM patients. A significant intervention × pathology × time interaction was observed for inflammatory mass size ( P < 0.001), with the most pronounced reduction in the GLM-KFX group during the first three months. Furthermore, KFX significantly reduced pain scores (mean difference: -1.01) and recurrence rates (OR = 0.24), while demonstrating a comparable safety profile to the control. Conclusions KFX irrigation is a safe and effective adjunctive therapy for ulcerative NPM. The findings indicate favorable effects on pain relief and recurrence prevention and suggest that pathological subtype may influence treatment responsiveness.