Efficacy and safety of Songjiao Dihuang Tang decoction for the dynamic/adaptive treatment of immune checkpoint inhibitor-associated myocarditis: study protocol and statistical analysis plan for a stop&go, multicentre, randomized, parallel-controlled, double-blind, superiority clinical trial.

Background: While immune checkpoint inhibitors (ICIs) enhance tumour therapy, immune checkpoint inhibitor-associated myocarditis (ICIAM) pose risks of mortality because of their low incidence and rapid progression. Existing guidelines focus mostly on tiered management, with corticosteroid therapy serving as the primary treatment for the mild stage. Preliminary data suggest that Songjiao Dihuang Tang (SJDHT) may shorten disease duration, alleviate symptoms, and reduce glucocorticoid use. However, prospective multicentre studies remain rare because of sample scarcity, underdiagnosis of early-stage cases, centre-specific variability, and rapid clinical evolution. Consequently, in this study patients with mild ICIAM based on 2020 Chinese Expert Consensus criteria were recruited and it follows the 2023 clinical implementation recommendations. This prospective, multicentre RCT aims to verify whether SJDHT combined with conventional treatment reduces the disease duration, progression, and mortality. Methods and analysis: In this 1:1 randomized controlled trial, 200 patients with mild IC-IAM will receive either SJDHT (30 mL bid for 28 days) or a placebo. Both groups will receive standard care: initial methylprednisolone (1-2 mg/kg/d), tapered by 25%-40% every 3-5 days, and a switch to oral equivalent prednisone at ≤40 mg (tapered by 5 mg/week until cessation). A "stop&go" adaptive design is employed to manage rapid disease progression, with assessments at 24-72 h, day 14, and day 28 after enrolment. Weekly cTn monitoring informs MDT-guided steroid tapering (if cTn decreases) or potential unblinding and endpoint triggering (if the cTn levels increases with a confirmed progression risk). Following the 28-day treatment, follow-ups are scheduled at months 1, 3, and 5 (6 months total). Parameters such as cTn, myocardial enzymes, ECG, echocardiography, symptoms, MACE, and safety will be recorded at each visit. The primary outcomes are the cTn recovery time and treatment efficacy rate. Secondary outcomes include the ICIAM progression rate, cardiac function indices, cancer-related symptoms, quality of life, MACEs, and TCM efficacy. The data will be analysed according to a predefined statistical plan, including missing data imputation and primary/secondary/safety outcome evaluations. Discussion: This research will contribute a standardized Traditional Chinese Medicine clinical research paradigm to the global community, potentially improving the prognosis and safety of cancer patients receiving immunotherapy. Clinical Trial Registration: https://itmctr.ccebtcm.org.cn/. Trial number: ITMCTR2025001424. Registered on 16 July 2025 (retrospectively registered). Registry name:Therapeutic Strategies and Evidence-Based Research of Traditional Chinese Medicine (TCM) for Subclinical and Mild Immune Checkpoint Inhibitor-Associated Myocarditis (ICIAM).