Objective
In this study, the efficacy of combined application of Electroacupuncture at the “Four Abdominal and Sacral Acupoints” and conventional treatment versus conventional treatment will be evaluated.
Trial design and setting
This study is a single-center, randomized controlled, assessor-blinded clinical trial which was devised following the Consolidated Standards of Reporting Trials (CONSORT) Statement recommendations [14]. The total study period for this trial is 8 weeks (Figure. 1), including 4-week treatment phase and 4-week follow-up phase.
It will be performed in GuangDong Second Hospital of Traditional Chinese Medicine. 90 patients who meet the eligibility criteria and sign an informed consent form will be randomly devided into two groups to receive either electroacupuncture at the Four abdominal and sacral acupoints plus conventional treatment or conventional treatment alone in a 1:1 ratio. Electroacupuncture will be performed 30 min per day, 5 days per week for 4 weeks. Doctors with more than 5 years of clinical experience will be allowed to perform the interventions. After 4 weeks, Outcome measurements including residual urine volume、proportions of participants with residual urine decline ≥ 50%、efficacy rate、proportion of patients with catheterization、Short-Form Health Survey Questionnaire (SF-36) and the incidence of recurrent symptomatic urinary tract infection will be analysed by doctors who was blind to the allocation of the patients. The flowchart of the trial is shown in Figure. 2.
Participants
Recruitment strategies
Inpatients at acupuncture departments in GuangDong Second Hospital of Traditional Chinese Medicine will be recruited mainly in this RCT. Additionally, posters will be put in the hospitals and a Chinese multipurpose social media named WeChat will be applied to recruit. Brief descriptions of eligible criteria, the free acupuncture treatments and the possible risks of the trial will be marked and all patients have the right to participate or drop out at any time, and will be required to sign the informed consent before the trial begin.
Eligibility criteria: inclusion criteria
The inclusion criteria will be as follows.
1.Meet the diagnostic criteria for Urinary Retention after SCI;
2.Aged 18-60 years old, male or female;
3.more than 300 ml residual urine were detected in their bladder;
4.patients had clear consciousness and difficulty in urination;
5.patients complained of distention and pain in lower abdomen;
6.signed informed consent.
The exclusion criteria will be as follows.
1.Urinary retention not induced by SCI;
2.Clinical course more than 1 year;
3.Combination of heart, liver or kidney failure endanger the safety of life at any time;
4.Younger than 18 years or older than 60 years;
5.Those who do not receive electroacupuncture therapy;
6.Women with pregnancy and lactation.
Randomization and allocation
Random numbers will be generated by the random number generator in the SPSS statistical software package (Version 22.0, SAS Institute Inc.). Another specified researcher who is not involved in the study was responsible for it.
The allocation of participants will be sealed in a sequentially numbered opaque envelope. If the participant meets the inclusion criteria and signs informed consent, the above specified researcher will sequentially give the sealed random number envelope to the physician, who will open the envelope and allocate the participant to either electroacupuncture at the Four abdominal and sacral acupoints plus conventional treatment group or conventional treatment alone group according to the random number.
Blinding
Because of the add-on study design, a single-blinded method will be used. While the participants and practitioners cannot be blinded, we blinded the outcome assessors, data manager, and statistics analyzer. The assessor will be instructed not to communicate with participants about the possibility of their treatment. James et al.’s blinding index will be evaluated after the completion of the study to evaluate the success of blinding [15].
Intervention
Study schedule
Treatment group intervention
Patients in the treatment group will receive both electroacupuncture combined with conventional treatment. Electroacupuncture manipulation was carried out in two steps: First, patients will be asked to take a supine position. Following disinfection of skin with 75% alcohol, bilateral “Shuidao” (ST28) acupoints、Guanyuan (RN4) acupoint and Zhongji (RN3) acupoint (Four abdominal acupoints) will be stimulated using disposable and stainless needles (75 mm long and 0.30 mm in diameter, Suzhou Huanqiu Acupuncture Medical Appliance, Suzhou, China), inserted to a depth of 40-55mm until needling sensation transmit towards perineum and bladder. Then needles in the acupoints of bilateral ST29 as well as the needles in the acupoints of RN3 and RN4 will be connected to an electrical stimulator (SDZ-V EA; Huatuo, Suzhou, China) with a frequency of 2/10 Hz and current of 1 mA for 15 min, respectively. Secondly, the patients were placed in prone position, four sacral points were selected with the two upper points are located by the two edges of the sacrum on a level with the fourth sacral foramina while the locations of the two lower points are about 1 cm bilateral to the tip of the coccyx (Fig. 3, cited from Wang et al). The two upper points were inserted perpendicularly to a depth of 60 to 70mm to produce a sensation referred to the urethra or the anus by stimulating the main trunk of the PN with disposable and stainless needles (75 mm long and 0.30 mm in diameter, Suzhou Huanqiu Acupuncture Medical Appliance, Suzhou, China). The lower points were inserted obliquely toward the ischiorectal fossa to a depth of 60 to 70mm to produce a sensation referred to the urethra by stimulating the perineal nerve with acupuncture needles of the same model. Then needles in the acupoints of bilateral two upper points as well as the needles in the acupoints of bilateral two lower points will be connected to an electrical stimulator (SDZ-V EA; Huatuo, Suzhou, China) with a frequency of 2/10 Hz and current of 1 mA for 15 min, respectively. Electroacupuncture was manipulated once daily, 5 times a week and lasted for 4 weeks.
Conventional treatment refers to clean intermittent catheterization (CIC), which was carried out as follows: First, clean the penis/vulva of patients and open the urethra, then lubricate the catheter and insert the catheter gently. Stop advancing the catheter until urine flow starts and remove the catheter until urine flow stops. CIC was carried 6-8 times per hour, which based on fluid intake and bladder capacity of patients. CIC coud be ceased if bladder residual urine volume is less than 100ml.
Control group intervention
Patients in control group will receive CIC treatment following the same protocol used in the treatment group. Electroacupuncture will not be administered.
Discontinuing interventions
The trial will be ceased if one of the following conditions appeared: (1) a serious poststroke complication arises; or (2) recurrent stroke or any other severe condition occurs leaving the patient in a critical condition.
Outcome measures
The primary outcomes are changes of residual urine volume at baseline、after the final treatment and 4 weeks after the final treatment. The secondary outcome measures will be the proportions of participants with residual urine decline≥50% and efficacy rate after 4 weeks’treatment, as well as the the proportion of patients with catheterization、Short-Form Health Survey Questionnaire (SF-36) and the incidence of recurrent symptomatic urinary tract infection at baseline、after the final treatment and 4 weeks after the final treatment.
Any adverse events, including acupoint hematoma, infection, dizziness and apostasies will be evaluated during the whole treatment by the researcher. If any severe adverse events occurring, acupuncture intervention will be ceased immediately and the principal investigator will be informed to take proper actions. 1 month will be followed up after the trial in case of subsequent adverse events.
Safety assessment
Any adverse events, including acupoint hematoma, infection, dizziness and apostasies will be evaluated during the whole treatment by the researcher. If any severe adverse events occurring, acupuncture intervention will be ceased immediately and the principal investigator will be informed to take proper actions. 1 month will be followed up after the trial in case of subsequent adverse events.
Sample size calculation
The trial is designed to determine the role of electroacupuncture at the Four abdominal and sacral acupoints for urinary retention in patients with SCI and prove that electroacupuncture at the Four abdominal and sacral acupoints combined with conventional treatment is superior to conventional treatment alone. Therefore, residual urine volume change will be used as an evaluation index. According to our previous pilot study, the change of residual urine volume before and after treatment in the treatment group was shown to be 194.00±16.91 (n = 5) and that in control group was 184.50±14.35 (n = 5). Sample size was estimated using the following formula:
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)
where n represents the number of samples required, n=n1+n2, Q1=n1/n, Q2=n2/n with a significance level (α=0.05) of a two-sided two-sample t-test and 80% power to detect a difference between the two groups. Thus, a total sample size of 90 patients will be recruited allowing for 10% of attrition, with 45 in each.
Statistical analysis
SPSS 20.0 (IBM SPSS Statistics, IBM Corp, Somers, New York, USA) will be used to analyze the data. Quantitative data will be presented as mean ± SD. GCS、Barthel and FuglMeyer scores will be conducted between the two groups by a superiority independent sample t-test with a 95% CI. The incidence of complications and adverse events will be compared by χ2 test. Any missing data will be replaced by the last measured value. For all analyses, P values of less than 0.05 will be considered statistically significant.
Quality control
Before the trial, all the acupuncturists、nurses and assessors will be trained strictly in order to guarantee homogeneity in the measurement data and ensure high-quality data results. The training content will include study protocol, diagnosis, inclusion and exclusion criteria, recording method of CRF, the location of the acupoints, acupuncture operation techniques, disposal of bleeding. All the study data will be recorded on the case report form. Dropouts and withdrawals from the study will be recorded in detail based on the intervention and follow-up periods. Data will be uploaded and verified by other two researchers who were not involved in the trial. This trial will be monitored by the Scientific Research Department of GuangDong Second Hospital of Traditional Chinese Medicine every one week.