Chemotherapy-induced nausea and vomiting (CINV) remains one of the most common and distressing adverse effects in patients receiving highly emetogenic chemotherapy (HEC). Despite the widespread use of guideline-recommended triple antiemetic therapy, a substantial proportion of patients continue to experience delayed-phase nausea and vomiting, which negatively affect treatment adherence, nutritional status, and quality of life. Effective strategies for improving delayed CINV control remain an important unmet clinical need. Auricular acupressure is a noninvasive traditional Chinese medicine intervention that has been widely used for the management of gastrointestinal symptoms and supportive care in patients with cancer. However, current evidence regarding its effectiveness in preventing CINV is limited by small sample sizes, methodological heterogeneity, and insufficient evaluation of delayed-phase outcomes. This multicenter, randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy and safety of auricular acupressure as an adjunct to standard triple antiemetic therapy for the prevention of CINV in patients receiving HEC. A total of 332 eligible participants will be randomly assigned in a 1:1 ratio to receive either auricular acupressure or sham auricular acupressure in addition to standard antiemetic treatment. The primary outcome is the complete protection rate during the delayed phase (24-120 hours) of the first chemotherapy cycle, defined as no vomiting, no use of rescue medication, and a nausea visual analogue scale (VAS) score below 25 mm. Secondary outcomes include complete protection, complete response, total control, nausea severity, vomiting episodes, rescue medication use, appetite changes, quality of life assessed by the Functional Living Index-Emesis (FLIE) and EORTC QLQ-C30, treatment adherence, and safety outcomes across multiple chemotherapy cycles. The findings of this study are expected to provide high-quality evidence regarding the role of auricular acupressure in the prevention of delayed CINV and support its integration into evidence-based supportive cancer care.
Chemotherapy-induced nausea and vomiting (CINV) remains one of the most common and distressing adverse effects experienced by patients receiving systemic anticancer therapy. Despite substantial advances in antiemetic prophylaxis, CINV continues to negatively affect nutritional status, treatment adherence, daily functioning, psychological well-being, and health-related quality of life. Patients receiving highly emetogenic chemotherapy (HEC), including anthracycline-cyclophosphamide-based regimens and cisplatin-containing regimens, remain at particularly high risk for both acute and delayed CINV. Current international antiemetic guidelines recommend prophylactic antiemetic therapy consisting of a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for patients receiving HEC. Although guideline-recommended regimens have substantially improved emesis control, delayed-phase CINV (24-120 hours after chemotherapy) remains insufficiently controlled in a considerable proportion of patients. Delayed nausea is particularly challenging to manage and is frequently associated with impaired oral intake, reduced quality of life, increased healthcare utilization, and decreased willingness to continue planned anticancer treatment. Therefore, the identification of effective adjunctive interventions for improving delayed-phase CINV control remains an important unmet clinical need. Auricular acupressure is a noninvasive intervention derived from traditional Chinese medicine. Through continuous stimulation of specific auricular acupoints, auricular acupressure may influence autonomic nervous system activity, gastrointestinal function, neuroendocrine regulation, and symptom perception. Auricular acupoint stimulation has been investigated as a complementary approach for the prevention and management of chemotherapy-induced nausea and vomiting in patients receiving anticancer treatment. Previous clinical studies and systematic reviews have suggested that auricular acupressure may improve chemotherapy-related nausea and vomiting and reduce symptom burden in patients with cancer. However, the currently available evidence remains limited by methodological heterogeneity, small sample sizes, inadequate sham-control procedures, insufficient blinding, and inconsistent outcome assessment methods. In particular, relatively few rigorously designed randomized controlled trials have specifically focused on delayed-phase CINV, which remains one of the most difficult aspects of antiemetic management. Consequently, high-quality evidence regarding the efficacy and safety of auricular acupressure as an adjunct to contemporary guideline-based antiemetic prophylaxis remains insufficient. The auricular acupoint prescription used in this study was developed in accordance with the auricular acupoint recommendations described in the 2025 Chinese Society of Clinical Oncology (CSCO) Guideline for the Prevention and Treatment of Antitumor Therapy-Induced Nausea and Vomiting. The intervention includes auricular acupoints such as Shenmen, Stomach, Sympathetic, and other protocol-specified points selected for the management of chemotherapy-induced nausea and vomiting. This study is designed as a multicenter, randomized, double-blind, sham-controlled clinical trial to evaluate the efficacy and safety of auricular acupressure as an adjunct to standard triple antiemetic therapy in patients receiving highly emetogenic chemotherapy. Eligible participants will be randomly assigned in a 1:1 ratio to receive either active auricular acupressure or sham auricular acupressure in addition to guideline-recommended antiemetic prophylaxis. The sham-controlled design is intended to minimize expectation bias and improve the internal validity of the study. The primary objective of this trial is to determine whether auricular acupressure improves delayed-phase control of chemotherapy-induced nausea and vomiting during the first cycle of highly emetogenic chemotherapy. The primary endpoint is the complete protection (CP) rate during the delayed phase (24-120 hours after chemotherapy), defined as no vomiting, no use of rescue antiemetic medication, and a nausea visual analogue scale (VAS) score below 25 mm. Compared with conventional endpoints that primarily focus on emesis control, complete protection incorporates both nausea severity and rescue medication use, thereby providing a more comprehensive assessment of clinically meaningful symptom control. Secondary objectives include the evaluation of complete protection, complete response, total control, nausea severity, vomiting outcomes, rescue medication use, appetite changes, patient-reported outcomes, health-related quality of life, treatment adherence, and safety outcomes across multiple chemotherapy cycles. Validated patient-reported outcome instruments, including the Functional Living Index-Emesis (FLIE) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), will be used to comprehensively assess symptom burden, functional impact, and quality of life. By employing a multicenter design, rigorous randomization procedures, double blinding, standardized intervention protocols, guideline-based antiemetic therapy, and validated outcome measures, this study seeks to address important limitations of previous research and generate robust clinical evidence regarding the effectiveness and safety of auricular acupressure for the prevention of chemotherapy-induced nausea and vomiting. The findings of this trial are expected to contribute to the evidence base for integrative symptom management and support the optimization of CINV prevention strategies in patients receiving highly emetogenic chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
332
Auricular acupressure will be administered using Vaccaria seed ear patches applied to protocol-specified therapeutic auricular acupoints, including Shenmen, Stomach, Sympathetic, and other designated points. Participants will be instructed to perform self-acupressure according to the study protocol during the intervention period
Sham auricular acupressure will be administered using identical Vaccaria seed ear patches applied to non-therapeutic auricular points located in the earlobe area. Participants will receive the same self-acupressure instructions and treatment schedule as those in the active intervention group.
The First Hospital of China Medical University
Shenyang, Liaoning, China
Complete Protection (CP) Rate During the Delayed Phase of Cycle 1
Complete protection (CP) during the delayed phase (24-120 hours after chemotherapy) in Cycle 1, defined as no vomiting, no use of rescue antiemetic medication, and a nausea visual analogue scale (VAS) score \<25 mm.
Time frame: 24 to 120 hours after chemotherapy administration in Cycle 1 (each chemotherapy cycle is approximately 21-28 days).
Complete Protection Rate During the Acute and Overall Phases of Cycle 1
Proportion of participants achieving complete protection during the acute phase (0-24 hours) and overall phase (0-120 hours) of Cycle 1, defined as no vomiting, no use of rescue antiemetic medication, and no significant nausea (VAS score \<25 mm).
Time frame: 0-24 hours and 0-120 hours after chemotherapy administration in Cycle 1(each chemotherapy cycle is approximately 21-28 days).
Complete Response Rate During Acute, Delayed, and Overall Phases of Cycle 1
Proportion of participants with no vomiting and no use of rescue antiemetic medication during the acute (0-24 hours), delayed (24-120 hours), and overall (0-120 hours) phases of Cycle 1.
Time frame: 0-120 hours after chemotherapy administration in Cycle 1, including acute phase (0-24 hours), delayed phase (24-120 hours), and overall phase (0-120 hours) (each chemotherapy cycle is approximately 21-28 days).
Total Control Rate During Acute, Delayed, and Overall Phases of Cycle 1
Proportion of participants with no vomiting, no rescue antiemetic medication use, and no nausea (VAS score \<5 mm) during the acute, delayed, and overall phases of Cycle 1.
Time frame: 0-120 hours after chemotherapy administration in Cycle 1, including acute phase (0-24 hours), delayed phase (24-120 hours), and overall phase (0-120 hours) (each chemotherapy cycle is approximately 21-28 days).
Appetite Loss Severity
Appetite loss assessed daily using a 4-point Likert scale (0-3). Changes from baseline and average appetite loss scores during the overall phase will be evaluated.
Time frame: Daily from Day 1 to Day 5 after chemotherapy administration in Cycle 1 (each chemotherapy cycle is approximately 21-28 days).
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