Zhengyuan capsules for the treatment of chemotherapy-induced cancer-related fatigue in stage IIIB–IV unresectable NSCLC: study protocol for a randomized, multi-center, double-blind, placebo-controlled clinical trial

BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) frequently experience cancer-related fatigue (CRF) during or after chemotherapy. Traditional Chinese medicine (TCM) can effectively relieve CRF, although the clinical evidence is insufficient due to the absence of extensive and rigorous clinical studies. Zhengyuan capsules have both tonifying and dispersing effects, and its ability to alleviate CRF has been verified in mice. This study aimed to provide evidence for the role of proprietary Chinese medicines in alleviating CRF in advanced NSCLC patients. METHODS: A multi-center, randomized, double-blind, placebo-controlled clinical trial has been designed to evaluate the efficacy and safety of Zhengyuan capsules for CRF in stage IIIB–IV unresectable NSCLC patients undergoing chemotherapy. Thirty eligible participants will be randomized into two groups at a 1:1 ratio during chemotherapy using the centralized interactive web response system. All patients will receive conventional platinum-based dual-drug chemotherapy and Zhengyuan capsules or simulant for 42 consecutive days starting on the first day of the first week of chemotherapy. The primary outcome is the difference between baseline and post-treatment CRF in the two groups, which will be assessed using the Brief Fatigue Inventory (BFI) score. Secondary outcome measurements include the Revised Piper’s Fatigue Scale (RPFS)-Chinese Version, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) v3.0 combined with EORTC QLQ-LC13 (Lung Cancer 13), clinical symptom score, hematology exploratory index, and progression-free survival. And safety indicators such as blood, urine, fecal routine, liver and kidney function, coagulation, and electrocardiogram will be performed before chemotherapy. Data will be analyzed according to intention-to-treat (ITT) and per-protocol (PP) principles; Empowerstats and R will be applied for statistical analysis. DISCUSSION: This trial will provide data on the efficacy and safety of Zhengyuan capsules for treating CRF in stage IIIB–IV unresectable NSCLC patients undergoing chemotherapy. It will also provide a basis for the feasibility of a large-scale clinical trial. TRIAL REGISTRATION: The clinical trial was registered on 19 November 2020 through https://www.chictr.org.cn (registration number: ChiCTR2000040061).