This trial is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. It has been approved by the Ethics Committee at Renmin Hospital of Wuhan University (approval number WDRY2017-K008). A patient information sheet will be given to patients who are willing to consider trial entry, and a written informed consent is obtained before they are included. The LVMRSTARRODS2017 trial has been registered at ClinicalTrials.gov [NCT03060330].
Study design
A single center, prospective, randomized controlled, parallel, and single-blind trial was designed. The LVMRSTARRODS2017 trial compares LVMR with or without STARR in women undergoing surgery for ODS. The overall design is shown in Fig. 1.
Study objectives
The aim of the study is to determine if LVMR combined with STARR helps patients with ODS more than LVMR alone. Patients are blinded and are not aware undergoing which group of procedures. For the surgeon performs the procedures and will see patients postoperatively, double blinding could not be guaranteed. However, with an independent masked evaluator performing the clinical assessment, the bias of a single-blind study will be corrected.
Primary endpoint
The primary study endpoint is defined as the rate of complications within 12 months after surgery.
Secondary endpoints
The secondary endpoints are defined as the percentage of changes in total ODS score (ODS-S), Patient Assessment of Constipation-Quality of Life score (PAC-QoL), the Health-Related Quality of Life Short Form Health Survey (SF-36) version 1, the Cleveland Clinic Fecal Incontinence Score (CCFI), the Fecal Incontinence Quality of Life Scale (FIQoL), between baseline and 1, 3, 6 and 12 months follow-up.
Eligibility criteria
Eligible patients are adults aged 18 years or older, no more than 70. The eligibility criteria are listed in Table 1.
Table 1 Eligibility criteria.
Inclusion criteria
| Exclusion criteria
|
· Patients affected by obstructed defecation with a minimum ODS score of 10
| · Full-thickness prolapse
|
· Have rectocele and/or rectal prolapse confirmed by defecography
| · Slow transit constipation
|
· Often experience excessive straining, sense of incomplete evacuation, and/or prolonged time for complete evacuation when attempting a bowel movement
| · Anismus
|
· Have experienced ODS symptoms for at least 12 months prior to enrollment
| · Pelvic organ prolapse
|
· Failure of at least 6 months of medical therapy
| · Previous rectal or anal surgery
|
· Have an American Society of Anesthesiologists (ASA) score of no more than 3
| · Recto-vaginal fistula
|
| · Pregnancy
|
| · Prior pelvic radiotherapy
|
| · Significant rectal fibrosis
|
| · Evidence of colorectal neoplasia, carcinoma, or inflammatory bowel disease
|
| · Perineal infection
|
Surgical intervention
All the procedures are performed by a single surgeon (TF). The LVMR technique used for this protocol is as previously described [18, 19]. Subjects randomized to this arm will receive a standard LVMR. Briefly, the peritoneum is opened over the right side of the sacral promontory. The mesorectum is dissected and extended in an inverted J-form along the right side. The rectovaginal septum is opened to the pelvic floor. Polypropylene mesh is pasted to the ventral aspect of the rectum with biological glue. The proximal end of the mesh is fixed on the anterior longitudinal ligament at sacral promontory with nonabsorbable sutures. The incised peritoneum is then closed to over the mesh. Subjects randomized to the LVMR with STARR arm will undergo a STARR procedure after a standard LVMR. Briefly, after finishing abdominal procedures, a circular anal dilator is then introduced into the rectum. The purse-string anoscope is used to complete a purse-string suture around the entire rectal ciecumference, about 2-3 cm above the haemorrhoidal apex. A 33-mm circular stapler is opened, inserted until crossing the purse-string which is then tied with a knot. Then the stapler is closed and fired.
Recruitment and trial timeline
Enrolling study participants was started in February 2017. The duration of the study for each patient is expected to be 12 months with follow-up at 1, 3, 6 and 12 months postoperatively.
Treatment assignment and randomization
Eligible patients receive information about participating in the trial by their surgeon. Consecutive eligible patients are randomly assigned to one of two groups with a 1:1 equal allocation ratio. An independent individual performs randomization using a software randomization program.
Assessments
Baseline
After recruitment and consent, the following baseline data will be obtained within one months after surgery (Table 2): demographic information, medical history, list of medications, and physical exam. The coherent and easily administered SF-36 is used as a generic measure of health-related quality of life [23]. The PAC-QoL and FIQoL are used for patients with constipation or fecal incontinence, respectively. Functional assessment is performed for constipation using the ODS-S, for fecal incontinence using the CCIS.
Data collection
Table 2 shows the timeline of visits, events and data collection.
Table 2 Schedule of study measures.
| Baseline
| Surgery
| 1 months
| 3 months
| 6 months
| 12 months
|
Window for collecting measure
| - 2 months
|
|
|
|
|
|
Informed consent
| ×
|
|
|
|
|
|
Demographics
| ×
|
|
|
|
|
|
Medical history
| ×
|
|
|
|
|
|
Medications
| ×
|
| ×
| ×
| ×
| ×
|
Physical exam
| ×
|
| ×
| ×
| ×
| ×
|
ODS-S
| ×
|
| ×
| ×
| ×
| ×
|
PAC-QoL
| ×
|
| ×
| ×
| ×
| ×
|
SF-36
| ×
|
| ×
| ×
| ×
| ×
|
CCFI
| ×
|
| ×
| ×
| ×
| ×
|
FIQoL
| ×
|
| ×
| ×
| ×
| ×
|
Defecography
| ×
|
|
|
| ×
| ×
|
Statistical analysis
Sample size
The LVMRSTARRODS2017 trial is a superiority trial with hypothesis that the LVMR plus STARR approach reducing the primary endpoint events. The sample size was calculated with combined results from published studies on LVMR. A systematic review shows that abdominal rectopexy results in a combined recurrence and complication rate of 20.8% [22]. A previous study showed 24.3% of the patients after LVMR developed symptomatic grade III/IV hemorrhoids requiring stapled or excisional hemorrhoidectomy. Taken together, these data indicate that the prevalence of all complications including symptomatic hemorrhoids is estimated to be 45%. Accordingly, it was calculated that a total of 92 patients (46 in each group) would be sufficient to detect an absolute risk difference of 15% for the primary endpoint with significance α = 5%, achieving a power of 1 − β = 80%. With an anticipated 10% rate of dropout and loss to follow-up, a total of 102 patients, equally divided into both groups, are allocated to the trial.
Statistical analysis plan
SPSS software version 20.0 is used for statistical analyses. Data will be presented as mean ± standard deviation, median and interquartile range, or number and percentage. Comparison of continuous variables is performed using unpaired t-test or Wilcoxon signed rank test. Chi-square test or Fisher’s exact test according to the expected counts is applied to compare categorical variables. For adjusted analysis, linear or logistic regression modeling is used for continuous or categorical outcome measures, respectively. In all cases, P < 0.05 is considered significant.