This will be a randomized, single-blind, parallel controlled study. Patients who meet the inclusion criteria will be divided into a treatment group and a control group, each with 36 patients. The treatment group will undergo modified ultrasonic scalpel haemorrhoidectomy, and the control group will undergo Milligan-Morgan operation and internal ligation injection. The study will be conducted at Shangjin Hospital of West China Hospital of Sichuan University.
Eligible participants who meet the diagnostic criteria for haemorrhoids in the Clinical Diagnosis and Treatment Guidelines for Hemorrhoids (2006 edition), formulated by the Colorectal and Anal Surgery Group of the Chinese Medical Association Surgery Branch and the Anorectal Branch of the Chinese Society of Traditional Chinese Medicine, will be enrolled. All the participants will have been treated and hospitalized by the Department of Integrated Traditional Chinese and Western Medicine of West China Hospital of Sichuan University. Recruitment began on July 1, 2021 and is expected to last for 24 months.
The trial was approved by the Ethics Committee on Biomedical Research at West China Hospital of Sichuan University (Approval code: NO. 2020-367). It was also registered in the Chinese Clinical Trial Registry (Registration ID: ChiCTR2100047229).
Patients with the clinical manifestation of mixed haemorrhoids with the symptoms of internal haemorrhoids and external haemorrhoids existing at the same time. Among them, internal haemorrhoids should be manifested as stage II (grade) or higher;
Patients aged 20-70 years without obvious surgical contraindications;
Patients who provide informed consent, with good compliance, and are able to cooperate to complete all clinical research content.
Patients with haemorrhoids combined with anusitis;
Patients with haemorrhoids combined with inflammatory bowel disease;
Patients with suppurative infection around the anorectal canal;
Patients with intestinal infectious diseases (e.g., dysentery);
Patients diagnosed with outlet obstructive constipation.
During the study, subjects have poor compliance, which can affect the effectiveness evaluation;
Those who have serious adverse events, complications and special physiological changes and are not able to continue the experiment;
Those who quit on their own during the study;
Patients who withdraw from the trial, are lost to follow-up or die due to various other reasons;
Those who have incomplete data which affect the validity judgement.
Recruitment and trial timeline
Researchers will recruit participants from the inpatient wards of the Department of Integrated Traditional Chinese and Western Medicine. After screening patients who met the inclusion and exclusion criteria, the researcher will inform the participants of the different treatment methods available for their condition, provide information about the study, and have the participants sign a written informed consent form. A copy will be kept by the participant, and the original will be kept in the hospital.
The participants who meet the criteria will be registered, the baseline data and clinical features of the participants will be collected before the operation, and measurements will be taken at each observation time node according to the CRF form after the operation (Table 1). Participants who met the withdrawal criteria shall strictly follow the criteria and provide records. The registration process, the intervention and evaluation schedule and the study flow chart are shown in Tables 1 and 2.
Table 1: Schedule of the registration process, the intervention, and evaluations
POD= postoperative day; W= week; M= month; VAS= visual analogue score; SF36= 36-Item Short Form Health Survey
Table 2: Flow chart of the research phases.
VAS= visual analogue score; SF-36= 36-Item Short Form Health Survey.
The number of cases in this test were estimated based on the count data of the test unit (n):
According to the loss to follow-up rate of 15%, the ratio of the control group and treatment group was 1:1, with 36 participants per group.
Randomization and blinding
A third party statistician will use Excel software (Kingsoft Office Software Co. Ltd. China) to randomly assign participants to the two study groups in equal proportions. Only one data administrator will be able to access the table of random numbers in the computer. Participants will be registered by the research assistant in the order of entry time. The data administrator will use the random number table for grouping. The two groups will receive different surgical methods, and the operator and observer must know which group the patient is assigned to, so they cannot be blinded. However, the patients and statisticians will be blinded to the allocation of the participants.
The treatment group
① The external haemorrhoids in the mother haemorrhoid area at points 3, 7 and 11 will be removed by ultrasonic scalpel in a V-shape;
② The internal haemorrhoids will be clamped with forceps to be removed, the superior haemorrhoids artery will be ligated with No. 0 mousse thread "8", 1 ml of Xiaozhilin will be injected under the ligation proximal sticking mould, and then the haemorrhoid will be removed it slowly with an ultrasonic scalpel along the clamp mark at the base;
③ The carbonization (fixation) range of the incision will be checked, the free carbonized tissue will be removed at the incision, a needle will be inserted at the edge of the solidified tissue to suture the incision with the figure of "8" slightly above the tooth line, and then the incision epithelium will be sutured near the tooth line with the modified "8" suture method. When there is no obvious bleeding from the wound, the operation will be complete.
The control group
① The top of the external haemorrhoids will be clamped and gently pulled outward to expose the internal haemorrhoids. A V-shaped incision will be made on the external haemorrhoids, and the subcutaneous tissue will be stripped to 0.2 cm on the tooth line. The stripped external haemorrhoids and the base of the internal haemorrhoids will be clamped with middle-curved forceps. No. 0 silk thread will be used to run through the base root of the suture clamp. Part of the internal haemorrhoid tissue will be removed, without letting the suture slip off.
② In the same way, the other haemorrhoids will be removed and ligated, and 3~55 ml of 1:1 Xiaozhiling (1 part Xiaozhiling stock solution, 1 part normal saline) will be injected into the mucosa of the superior haemorrhoid artery area where the haemorrhoids are ligated under an anoscope to prevent bleeding. When there is no obvious bleeding from the wound, the operation will be complete.
Perioperative management, discharge, and follow-up
After the operation, a fluid diet will be given for 1 day, and appropriate fluids will be supplemented. Nonsteroidal anti-inflammatory drugs or opioid central analgesics will be given for postoperative pain according to the VAS pain score. For postoperative urinary retention, catheterization will be determined by the ward doctor on duty after evaluating the patient's symptoms and signs. The patient's catheter will be removed on POD 2. For postoperative defecation, lactulose oral solution will be used to soften the stool on the first day after the operation. If the patient still has difficulty with defecation, a glycerine enema can be given to help the patient defecate. If the symptoms still cannot be alleviated, a warm normal saline can be given to clean the enema.
Twenty-four hours after the operation, the anal canal dressing will be removed, and the patient can defecate on their own. After defecation, the patients will be treated with heat-clearing and detoxifying traditional Chinese medicine sit-baths, iodophor disinfection, indomethacin and furazolidone embolization of the anus, and dressing changes every day after defecation. The patient's wound recovery, stool smoothness and blood in the stool will be evaluated to decide to arrange for discharge. After discharge, the patient will be advised not to exercise vigorously, continue perianal disinfection and dressing changes, and participate in regular outpatient follow-up. Wound healing and surgical complications will be observed 1, 2, 3 and 4 weeks after the operation.
Each participant will be followed up 12 and 24 weeks after the operation via WeChat, telephone, video and outpatient clinics. At 3 months and 6 months after the operation, the Cleveland Clinic Florida Fecal Incontinence Score (CCF-FI) will be used to evaluate the anal condition of the patients and to evaluate whether the patients have postoperative anal incontinence. The simple SF-36 quality of life questionnaire (self-made) will be used to evaluate the patients half a year after operation.
For the schedule of the trial, please see Table 1.
Primary outcome measures
The primary outcome measures are postoperative incision healing time and recovery time of the patients, calculated in days (d).
Efficacy evaluation: Efficacy will be evaluated according to the efficacy evaluation of mixed haemorrhoids in the 2017 Standard for Diagnosis and Efficacy of TCM Diseases and Syndromes as follows: Cured: the symptoms and haemorrhoids disappear; Improvement: the symptoms improve and the haemorrhoids shrink; and Unhealed: there are no changes in symptoms and signs.
Secondary outcome measures
Postoperative complications: pain: A visual analogue scale (VAS) will be used to observe the patients’ pain 4 h, 8 h and 24 h after operation and the pain from defecation for 7 consecutive days after the operation in the two groups. Urinary retention will be assessed by the "with" and "without" method. Postoperative bleeding will be assessed as follows: 0 points: no bleeding; 1 point: blood on the paper; 2 points: drops of blood; 3 points: ejection of blood; and 4 points: Massive bleeding that requires surgery to stop the bleeding. Postoperative oedema will be assessed as follows: 0 points: no oedema; 1 point: oedema in 1/4 of the anal margin incision; 2 points: oedema in 1/2 of anal margin incision; 3 points: oedema in 3/4 of the anal margin incision; and 4 points: oedema around the perianal incision. Anal stenosis will be assessed by the "with" and "without" method.
Anal function evaluations 3 months and 6 months after operation: Anal function evaluation will be assessed by the CCF-FI as follows: normal continence: the anus controls stool, intestinal fluid and intestinal gas is normal; partial anal incontinence: the anus cannot control intestinal fluid, intestinal gas, loose stools, or the pollution of underwear or the anus has a sense of dampness; and Complete incontinence: the anus cannot control forming stool.
Evaluation of quality of life half a year after the operation: The simple SF-36R quality of life questionnaire (self-made) will be used for evaluating the quality of life.
Evaluation of patient satisfaction rate half a year after the operation: The self-designed patient satisfaction questionnaire will be used, which is divided into very satisfied, satisfied, general and no opinion, and calculates the percentages of the 4 levels.
Safety and reporting of serious adverse events
In this study, adverse events will be defined as any treatment-related medical event, including any adverse and unexpected signs, symptoms or illnesses associated with the treatment. Adverse events will be evaluated according to the Standard for General Terminology for Adverse Events (V4.03). Within 24 hours after the occurrence of adverse events, the researchers and relevant experts will evaluate and classify the events and deal with them in a timely manner according to the condition. We will collect, evaluate, and report any spontaneously described adverse events that occur among the participants. Adverse event data regarding the severity of the occurrence, duration (signs and symptoms) of the adverse reactions, and how to resolve (or not) them during treatment will be recorded. If the participants experience serious adverse events, they will be reported to the principal investigator and the Ethics Committee of West China Hospital of Sichuan University (IEC) and it will be decided whether blindness is removed and if they withdraw from the study.
Data collection and management
The case report form (CRF) includes observation time points, outcome measurements, adverse events, and safety assessments. The evaluators of the results will follow the requirements of the CRF and fill in relevant information in a timely and accurate manner. Data collection and entry will be carried out independently by two staff members and completed by a third staff member. The principal investigator will not be involved in data collection. Data will be obtained from the CRF, and only trial group members will be able to access the CRF and perform dual data entry. The organization of the test is as follows. The steering committee will fully oversee the design of the study. The investigators of the Data Management Safety Committee (DMSC) will supervise and confirm that the CRF is completed correctly and that the data are consistent with the original data. If there are any errors or omissions, the investigator will immediately correct them. We do not intend to collect personal information about potential or registered participants other than that typically collected during hospitalization. For confidentiality, the electronic health information will be encrypted in accordance with the hospital’s protocol. After the trial, personally identifiable information will be omitted and placed in a separate database for data analysis.
Data analysis: We will use SPSS software version 17.0 (IBM, Armonk Company, New York, USA) for data analysis. Demographic and baseline data will be analysed using standard descriptive statistics. For categorical variables, Fisher's exact test will be used. For continuous variables, Student's t test or the Mann–Whitney U test will be used. The entire data analysis process will be performed by statisticians who are independent of the research team and are blinded to the set. The acceptable level of significance for all analyses will be p < 0.05.
The ethics committee will locally monitor the quality of the trial after the first batch of patients is registered. The trial management team will meet every 3 months to check the implementation of the study, including the recruitment rates, the data quality and adverse event reporting.
Plans for communicating important protocol amendments to relevant parties
The protocol, statistical analysis plan, data safety management plan, informed consent, and recruitment materials were reviewed and approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University. Any subsequent modifications will be submitted for review, and annual safety and progress reports will be submitted. In addition, the online trial registration form will be updated accordingly. The data can be obtained through the research centre upon reasonable request.
The research results will be disseminated through peer-reviewed publications and speeches at industry academic conferences. A summary of the research results will be released through WeChat, Weibo and other social media platforms.