Shenqi Shiyiwei Granule for breast cancer related fatigue-centered symptom cluster: protocol of a multicenter randomized double-blind placebo-controlled trial

A multicenter, randomized, double-blind, placebo-controlled study protocol will evaluate whether Shenqi Shiyiwei Granule improves a fatigue-centered symptom cluster in postoperative breast cancer survivors. The trial is designed to measure treatment effects, and no efficacy results are available yet.

Researchers plan to enroll 262 women at 11 hospitals across China. Participants will be 18 to 75 years old, have stage I to IIIA hormone receptor-negative breast cancer without signs of recurrence or metastasis, and have completed surgery followed by at least three months of adjuvant or intensified adjuvant therapy. They must also have an ECOG performance status of 0 or 1.

Eligibility requires a moderate-to-severe fatigue-centered symptom cluster as defined by the protocol: fatigue, shortness of breath and pain must each score at least 1, while their mean score must be at least 4 on the Chinese version of the MD Anderson Symptom Inventory. Participants must also meet prespecified traditional Chinese medicine symptom criteria for weakness.

After written informed consent, participants will be randomized 1:1 to receive Shenqi Shiyiwei Granule or matching placebo for 60 days. Both groups will receive standardized psychological, exercise and dietary guidance across a 120-day study period comprising a 60-day intervention and a 60-day observation period. Block randomization and a central interactive web response system will conceal treatment assignment from investigators and participants.

The primary outcome is the change from baseline in the mean fatigue, shortness-of-breath and pain score at two months, with assessments planned every 15 days during treatment. Secondary outcomes include fatigue and quality-of-life measures, a traditional Chinese medicine Spleen Qi Deficiency scale and cardiopulmonary functional capacity assessed by cardiopulmonary exercise testing.

Safety monitoring will include vital signs, complete blood count, urinalysis, stool testing, liver and kidney function tests, tumor markers and electrocardiography. Exploratory analyses will measure hypothalamic-pituitary-adrenal-axis hormones, cytokines and gonadal hormones to examine possible biological mechanisms associated with the symptom cluster.

The primary efficacy analysis will use mixed-effects models for repeated measures. The principal contrast is the between-group difference at month two, with a two-sided significance level of 5% and 95% confidence intervals. Sensitivity analyses are planned to examine how departures from the missing-at-random assumption could affect results, while subgroup analyses will explore effects by baseline symptom severity, tumor stage, age and concurrent other therapy.

The protocol describes subgroup analyses as hypothesis-generating and does not control for multiplicity. The primary analysis population will include all randomized participants according to assigned treatment, while per-protocol and safety populations are also prespecified. Ethics approval was granted by the Institutional Ethics Committee of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University.

Because this is a study protocol, it does not establish whether Shenqi Shiyiwei Granule is more effective or safer than placebo for this population, and no conclusion about efficacy or safety can yet be drawn.

Subject of Research: Protocol for a randomized trial of Shenqi Shiyiwei Granule in breast cancer survivors with fatigue-centered symptoms

Article Title: Shenqi Shiyiwei Granule for breast cancer related fatigue-centered symptom cluster: protocol of a multicenter randomized double-blind placebo-controlled trial

Article References: Li, S.-Y., Wu, T.-T., Zhang, Y.-X., Zhao, J., Hu, J., Zhang, G.-L., & Yang, G.-W. (2026). Shenqi Shiyiwei Granule for breast cancer related fatigue-centered symptom cluster: protocol of a multicenter randomized double-blind placebo-controlled trial. Frontiers in Oncology, 16, Article 1941699. https://doi.org/10.3389/fonc.2026.1941699

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1941699

Keywords: breast cancer, cancer survivors, fatigue, dyspnea, pain, symptom cluster, herbal medicine, randomized controlled trial, clinical trial protocol, Shenqi, Shiyiwei, Granule