Early Electroacupuncture for Post-TURP LUTS

II. Research Content 1. Research Objectives This is a prospective study designed to evaluate the effect of early electroacupuncture intervention on lower urinary tract symptoms (LUTS) after benign prostatic hyperplasia (BPH) surgery.

• Research Content

• Selection of research site This study will be conducted in the Department of Urology, Zhongda Hospital Affiliated to Southeast University.
• Selection of research subjects Information of patients receiving acupuncture intervention and patients in the control group will be retrieved from the electronic medical record system. Patients meeting the inclusion and exclusion criteria will be screened, and allocated to the treatment group or the control group at a 1:1 ratio via block randomization, receiving electroacupuncture intervention or sham acupuncture intervention respectively, before being enrolled in the clinical trial.

Number of enrolled subjects:

144 cases from the Department of Urology, Zhongda Hospital Affiliated to Southeast University

Sample size calculation:

This study is a prospective, multicenter, randomized, placebo-controlled clinical trial aimed at evaluating the efficacy of early electroacupuncture intervention in improving LUTS after transurethral resection of the prostate (TURP) and holmium laser enucleation of the prostate (HoLEP). The Primary Endpoint is defined as the International Prostate Symptom Score (IPSS) obtained one week after catheter removal. This estimation is based on the two-sample t-test for independent means, with required parameters including the expected mean difference between groups (δ), within-group standard deviation (σ), type I error probability (α), and type II error probability (β). We set the two-sided significance level α=0.05 and statistical power (1-β)=0.80, with a 1:1 sample size allocation ratio between the two groups (treatment group vs. sham acupuncture group).

Given the absence of perfectly matched studies that focus on male patients after TURP, compare electroacupuncture with sham acupuncture, and take IPSS score as the primary endpoint, we set the expected moderate effect size d=0.5. Based on the aforementioned parameters and the sample size calculation formula for comparing means of two independent samples:

n=2(Z1-α/2+Z1-β)2d2 Calculation results show that to achieve 80% statistical power, at least 64 subjects are required per group.

Considering the short intervention cycle and clear follow-up nodes of this study, we estimate that approximately 10% of subjects may be lost to follow-up or drop out for various reasons. To compensate for this sample loss, the adjusted number of subjects to be recruited per group is 64/(1-0.10)≈71.11. After rounding up, 72 subjects are required per group.

In conclusion, this study plans to enroll a total of 144 subjects (72 in the treatment group and 72 in the control group). This sample size is sufficient to statistically validly test the core hypothesis of this study, and meanwhile has good feasibility under the framework of multicenter collaboration. During the mid-study period, the need for sample size adjustment will be evaluated based on actual enrollment status and data variability.

(3) Research Period June 1, 2026 - June 1, 2027 Extraction and Allocation Method of Research Subjects This study adopts a prospective, randomized controlled design, and consecutively enrolls eligible post-prostatectomy patients during the study period who meet all inclusion criteria, do not meet any exclusion criteria, and voluntarily sign the informed consent form. To ensure the scientificity and rigor of the allocation process, random allocation is performed using mixed blocks with sizes of 4 and 6, to maintain a close dynamic balance in the number of participants between the treatment group and the control group at any stage of the study. To achieve allocation concealment, the random sequence will be generated by an independent statistician who does not participate in clinical work and deployed in a secure central randomization system. On-site researchers can only obtain the grouping result through the system after the patient is officially enrolled, thereby eliminating selection bias. This study plans to randomly allocate a total of 144 subjects to the treatment group and the control group at a 1:1 ratio.

Informed Consent of Research Subjects Sign the informed consent form (6) Outcome Measures Follow-up of urinary continence will be conducted at 1 week, 4 weeks, 8 weeks, and 12 weeks after catheter removal.

• Primary endpoint: International Prostate Symptom Score (IPSS) at 1-week follow-up after catheter removal.

• Uroflowmetry parameters (Qmax, voided volume, post-void residual urine volume [PVR])

• The International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) score at 1 week, 4 weeks, 8 weeks, and 12 weeks after catheter removal, to evaluate patients' LUTS and their impact on quality of life; ④ The Self-Rating Anxiety Scale (SAS) score is used to evaluate the potential improvement effect of acupuncture intervention on patients' psychological status; ⑤ Patients are required to keep a voiding diary at each follow-up node to comprehensively evaluate urinary function.

(7) Intervention Protocol All patients undergo catheter removal on postoperative day 5-7 (POD 5-7). Early electroacupuncture intervention (including verum electroacupuncture and sham electroacupuncture) is initiated on postoperative day 2 (POD 2), with one additional session each on POD 4 and POD 6, totaling 3 sessions.

The treatment group receives electroacupuncture at acupoints including Zhongji (RN3), Qihai (RN6), and Shuidao (ST28, bilateral) for 30 minutes per session, with the entire intervention course lasting one week. Continuous wave electroacupuncture is used, with an initial frequency of 2Hz. The intensity is gradually increased until the patient feels comfortable; the current intensity ranges from 1 to 5mA, which is gradually increased up to the maximum intensity that the patient can tolerate. The control group uses non-invasive sham acupuncture needles: validated non-penetrating needles with blunt tips (such as Park needles or Streitberger needles) are adopted. When pressure is applied to these needles, the tip retracts into the needle handle, which creates a tactile pressure sensation on the patient's skin without puncturing the skin. The intervention is performed at non-acupoints (points 1-2 cm adjacent to the verum acupoints, not located on the same meridian). The electrode clips of the electroacupuncture device are also attached to the handles of the sham acupuncture needles, and the device is turned on (producing the same sound and indicator light as in the treatment group) but outputs no current. In this way, the entire treatment scenario remains consistent with that of the verum treatment group in terms of vision and hearing.

To ensure all research subjects receive consistent standard postoperative rehabilitation guidance and control potential confounding variables, all patients successfully enrolled in this study (regardless of their group allocation) will receive a standardized nursing protocol after surgery.

• Research Methods

• Study Design This trial adopts the design scheme of randomized controlled prospective study.
• Inclusion and Exclusion Criteria

The inclusion criteria for subjects are as follows:

• BPH patients who have undergone TURP or HoLEP;
• Aged between 50 and 85 years;
• Signed informed consent.

The exclusion criteria for subjects are as follows:

• Pathological results confirm prostate tumor;
• History of lower urinary tract cancer including prostate cancer and bladder cancer in the past 5 years;
• Currently receiving or have received treatments with similar mechanisms to acupuncture (such as electroacupuncture, warming moxibustion, needle warming moxibustion, etc.) within 6 months prior to enrollment;
• Preoperative uncontrolled urinary system infection (asymptomatic lower urinary tract infection is excluded);
• Confirmed severe heart diseases including severe arrhythmia, severe cardiac insufficiency, acute myocarditis, constrictive pericarditis, pericardial tamponade, severe valvular disease, and heart failure;
• Confirmed liver injury or potentially severe liver disease (ALT or AST > 10 times the upper limit of normal);
• Confirmed severe renal impairment (eGFR < 25mL/min/1.73m2), or patients on planned or ongoing dialysis, or patients with acute contrast-induced nephropathy at screening;
• Confirmed dysfunction of other vital organs or severe primary diseases such as hematopoietic system diseases;
• Confirmed coagulation dysfunction (with typical clinical diagnosis or clear laboratory test results);
• Patients with mental illness or cognitive impairment; patients with severe depression, alcohol dependence, or a history of drug abuse;
• Patients judged by the investigator as unsuitable for participating in this study, or with high risk of dropping out, such as frequent changes of working environment that easily lead to loss to follow-up;

• Survival period estimated by the investigator to be ≤ 6 months; 14. Currently participating in other clinical trials. (3) Enrollment and Intervention Protocol: Information of postoperative patients will be retrieved from the electronic medical record system of Zhongda Hospital. Patients meeting the inclusion and exclusion criteria will be screened. After signing the informed consent form, patients are allocated to groups via randomization, and receive electroacupuncture intervention or sham acupuncture intervention respectively. The trial intervention protocol is as follows: All patients undergo catheter removal on postoperative day 5 (POD5). Early electroacupuncture intervention (including verum electroacupuncture and sham electroacupuncture) is initiated on postoperative day 2 (POD 2), with one additional session each on POD 4 and POD 6, totaling 3 sessions.

The treatment group receives electroacupuncture at acupoints including Zhongji (RN3), Qihai (RN6), and Shuidao (ST28, bilateral) for 30 minutes per session, with the entire intervention course lasting one week. Continuous wave electroacupuncture is used, with an initial frequency of 2Hz. The intensity is gradually increased until the patient feels comfortable; the current intensity ranges from 1 to 5mA, which is gradually increased up to the maximum intensity that the patient can tolerate. The control group uses non-invasive sham acupuncture needles: validated non-penetrating needles with blunt tips (such as Park needles or Streitberger needles) are adopted. When pressure is applied to these needles, the tip retracts into the needle handle, which creates a tactile pressure sensation on the patient's skin without puncturing the skin. The intervention is performed at non-acupoints (points 1-2 cm adjacent to the verum acupoints, not located on the same meridian). The electrode clips of the electroacupuncture device are also attached to the handles of the sham acupuncture needles, and the device is turned on (producing the same sound and indicator light as in the treatment group) but outputs no current. In this way, the entire treatment scenario remains consistent with that of the verum treatment group in terms of vision and hearing.

To ensure all research subjects receive consistent standard postoperative rehabilitation guidance and control potential confounding variables, all patients successfully enrolled in this study (regardless of their group allocation) will receive a standardized nursing protocol after surgery.

Efficacy Evaluation:

• Primary endpoint: International Prostate Symptom Score (IPSS) at 1-week follow-up after catheter removal.

• Uroflowmetry parameters (Qmax, voided volume, post-void residual urine volume [PVR])

• The International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) score at 1 week, 4 weeks, 8 weeks, and 12 weeks after catheter removal, to evaluate patients' LUTS and their impact on quality of life;

④ The Self-Rating Anxiety Scale (SAS) score is used to evaluate the potential improvement effect of acupuncture intervention on patients' psychological status;

⑤ Patients are required to keep a voiding diary at each follow-up node to comprehensively evaluate urinary function.

(4) Statistical Analysis: Statistical analysis will be performed by professional statisticians from the Center for Clinical Evaluation and Analysis, Zhongda Hospital Affiliated to Southeast University, using SPSS Statistics (V.26.0) or R language. All analyses will follow the intention-to-treat (ITT) principle. Shapiro-Wilk test is used to assess the normality of data distribution in data processing; imbalance in baseline demographic and clinical characteristics will be adjusted via analysis of covariance (ANCOVA); normally distributed continuous variables will be expressed as mean ± standard deviation; non-normally distributed continuous variables and ordinal variables will be expressed as median (interquartile range); categorical variables will be expressed as count and percentage; for missing data of primary and secondary endpoints, multiple imputation will be used for processing, and the primary analysis will be performed based on the imputed dataset. Meanwhile, a series of sensitivity analyses will be conducted to evaluate the impact of different missing data processing methods on the robustness of research conclusions.

Inclusion criteria

• Patients with benign prostatic hyperplasia (BPH) who have undergone transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP);
• Aged between 50 and 85 years;
• Provided signed informed consent.

Exclusion criteria

• Pathological examination results confirm the presence of prostatic tumors;
• History of lower urinary tract cancers including prostate cancer and bladder cancer within the past 5 years;
• Currently receiving or have received treatments based on principles similar to acupuncture within 6 months prior to enrollment, such as electroacupuncture, warm moxibustion, and warm needling moxibustion;
• Presence of uncontrolled urinary system infection before surgery (asymptomatic lower urinary tract infection is excluded);
• Diagnosed with severe cardiac conditions including severe arrhythmia, severe cardiac insufficiency, acute myocarditis, constrictive pericarditis, pericardial tamponade, severe valvular heart disease, and heart failure;
• Confirmed liver injury or potentially severe liver disease (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 10 times the upper limit of normal);
• Confirmed severe renal impairment (estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73m²), scheduled for or currently undergoing dialysis, or diagnosed with acute contrast-induced nephropathy during screening;
• Confirmed severe primary diseases such as dysfunction of other vital organs or diseases of the hematopoietic system;
• Confirmed coagulation dysfunction (with definite clinical diagnosis or clear laboratory test results);
• Patients with mental illness or cognitive impairment; patients with severe depression, alcohol dependence, or a history of drug abuse;
• Patients considered unsuitable for participation in this study by the investigators, or patients with factors strongly associated with study dropout, such as frequently changing working environments that increase the risk of loss to follow-up;
• Survival period estimated to be ≤ 6 months by the investigators;
• Currently participating in other clinical trials.