Effect of Auricular Acupressure Added to Standard Triple Antiemetic Therapy for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Multicenter Randomized Double-Blind Sham-Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 332
- 试验地点
- 1
- 主要终点
- Complete Protection (CP) Rate During the Delayed Phase of Cycle 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Participants, investigators, outcome assessors, data managers, and statisticians will remain blinded to treatment allocation throughout the study. Only trained traditional Chinese medicine (TCM) physicians administering the interventions will know treatment assignments and will not be involved in outcome assessment, data management, or statistical analysis. Active and sham auricular acupressure will use identical Vaccaria seed ear patches and treatment schedules. Participants in both groups will receive identical instructions regarding self-acupressure procedures and frequency. Allocation codes will be maintained by an independent statistician until completion of the final analysis unless unblinding is required for participant safety.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years, either sex.
- •Malignant solid tumor confirmed by histopathology.
- •③ Chemotherapy-naïve, planned to receive a single-day intravenous highly emetogenic chemotherapy (HEC) regimen, including:
- •Cisplatin-containing regimens (dose ≥50 mg/m²);
- •Anthracycline plus cyclophosphamide (AC/EC) regimens;
- •Carboplatin AUC ≥4;
- •Other highly emetogenic chemotherapy regimens recognized by guidelines.
- •④ In accordance with guideline recommendations for HEC regimens, the triple regimen of NK-1 RA + 5-HT₃ RA + dexamethasone is used:
- •⑤ ECOG performance status score 0-
- •⑥ Life expectancy ≥ 6 months.
- •⑦ Voluntarily signed informed consent, and able to understand and complete the patient diary.
排除标准
- •Nausea or vomiting already present within 24 hours prior to enrollment.
- •Symptomatic brain metastases, gastrointestinal obstruction, or other organic diseases likely to cause nausea and vomiting.
- •Local skin breakdown, infection, or deformity of the auricle, or allergy to adhesive tape/Vaccaria seeds (Wang Bu Liu Xing).
- •④ Planned use of olanzapine, thalidomide, or other antiemetic agents not specified in the protocol as part of the routine prophylactic antiemetic regimen during this chemotherapy cycle (i.e., those receiving a quadruple regimen or other non-standard prophylactic regimens).
- •⑤ Long-term regular use (e.g., more than 3 times per week) of benzodiazepines, antipsychotics, or sedative-hypnotics; or known history of drug abuse/dependence.
- •⑥ Severe mental illness or cognitive impairment that precludes cooperation with assessments.
- •⑦ Receipt of ear acupuncture or auricular acupressure (ear seeds) within 4 weeks prior to enrollment.
- •⑧ Pregnant or lactating women.
研究组 & 干预措施
Auricular Acupressure Group
Participants assigned to this arm will receive active auricular acupressure in addition to guideline-recommended triple antiemetic prophylaxis during highly emetogenic chemotherapy. 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 throughout the intervention period.
干预措施: Auricular Acupressure (Other)
Sham Auricular Acupressure Group
Participants assigned to this arm will receive sham auricular acupressure in addition to guideline-recommended triple antiemetic prophylaxis during highly emetogenic chemotherapy. Vaccaria seed ear patches identical in appearance to those used in the active intervention will be applied to non-therapeutic auricular points located in the earlobe area. Participants will receive the same instructions regarding self-acupressure procedures and frequency as those in the active intervention group
干预措施: Sham Auricular Acupressure (Other)
结局指标
主要结局
Complete Protection (CP) Rate During the Delayed Phase of Cycle 1
时间窗: 24 to 120 hours after chemotherapy administration in Cycle 1 (each chemotherapy cycle is approximately 21-28 days).
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.
次要结局
- Complete Protection Rate During the Acute and Overall Phases of Cycle 1(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(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(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(Daily from Day 1 to Day 5 after chemotherapy administration in Cycle 1 (each chemotherapy cycle is approximately 21-28 days).)
研究者
Xiujuan Qu
Professor and Chief Physician
First Hospital of China Medical University