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Anal Dilatation Plus Probiotics Before Ileostomy Reduction for Low Anterior Resection Syndrome

Phase 2
Conditions
Low Anterior Resection Syndrome
Interventions
Other: Anal dilatation per anus
Drug: administration of probiotics (Clostridium butyricum TO-A; Bacillus mesentericus TO-A; Streptococcus faecalisT-110) per anus
Registration Number
NCT04688242
Lead Sponsor
Sixth Affiliated Hospital, Sun Yat-sen University
Brief Summary

This is randomized, phase 2 trial in patients with rectal cancer undergoing sphincter-preserving proctectomy and temporary ileostomy, to explore the effects of anal dilatation plus probiotics administered per anus before ileostomy reduction in relieving postoperative bowel dysfunction known as low anterior resection syndrome (LARS).

Detailed Description

Approximately 60-90% of patients undergoing sphincter-sparing proctectomy complain of postoperative bowel dysfunction including incontinence, frequency, clustering, and urgency, collectively known as low anterior resection syndrome (LARS). Literatures and our previous data have demonstrated that diverting ileostomy is an independent risk factor for major LARS. This is a randomized, phase 2 trial in patients with rectal cancer who underwent sphincter-preserving proctectomy and ileostomy. This study will explore the effects of anal dilatation plus probiotics administered per anus in relieving the symptoms of LARS.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
164
Inclusion Criteria
  1. A voluntarily signed and dated informed consent form;
  2. ECOG Performance status is 0 or 1;
  3. Age at enrollment is of 18 to 80 years old.;
  4. R0 sphincter-preserving proctectomy and temporary ileostomy for rectal cancer;
  5. The distance from anastomosis to anal verge is ≤7cm;
  6. Both the anastomosis and the ileostomy is intact at 2 weeks follow-up after proctectomy;
  7. Baseline LARS score before proctectomy is <30;
  8. The preoperatively predicted LARS (POLARS) score after proctectomy is ≥28.
Exclusion Criteria
  1. R1/R2 resection or untreated metastases;
  2. Any synchronous or metachronous malignancies, except for cancers that have received curative treatment and have not recurred for more than 5 years, or carcinoma in situ that have been cured by appropriate treatment;
  3. Severe morbidity with life expectancy less than 2 years;
  4. Any toxicity of CTCAE grade 2 or above due to previous treatment that have not resolved, except for anemia, alopecia, skin pigmentation;
  5. Anastomotic leak within 2 weeks after proctectomy, suspected by clinical symptoms, digital rectal examination, or imaging;
  6. Complications of the ileostomy within 2 weeks after proctectomy, leading to premature takedown of the stoma (within 2 months after surgery);
  7. Any medical condition that may affect the safety and compliance of the subject.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment ArmAnal dilatation per anusAnal dilatation plus probiotics per anus Q3D, starting from 2 weeks after proctectomy until reduction of ileostomy.
Treatment Armadministration of probiotics (Clostridium butyricum TO-A; Bacillus mesentericus TO-A; Streptococcus faecalisT-110) per anusAnal dilatation plus probiotics per anus Q3D, starting from 2 weeks after proctectomy until reduction of ileostomy.
Primary Outcome Measures
NameTimeMethod
Major LARS at 1 years after proctectomyAt 1 years after proctectomy

Proportion of patients with Low anterior resection syndrome (LARS) score ≥30. LARS score is a tool consisting of five items, which are as follows: incontinence due to flatus (score range from 0 to 7), incontinence due to liquid stools (score range from 0 to 3), frequency of bowel movements (score range from 0 to 5), clustering (score range from 0 to 11) and urgency (score range from 0 to 16). The severity of each item is calculated on a scale ranging from 0 to 42, with a score of 0-20 (no LARS), 21-29 (minor LARS) and 30-42 (major LARS).

Secondary Outcome Measures
NameTimeMethod
Presence of stoma at 1 years after proctectomyAt 1 years after proctectomy

Proportion of patients with a stoma due to failure to reduce, or a second stoma after ileostomy reduction is assessed by a professional doctor or nurse at 2 years after proctectomy.

Anastomotic complications within 1 years after proctectomyWithin 1 years after proctectomy

Anastomotic complications is assessed by a professional doctor using Common Terminology Criteria for Adverse Events (CTCAE) classification.

LARS score at 1 years after proctectomyAt 1 years after proctectomy

Low anterior resection syndrome (LARS) score is a tool consisting of five items, which are as follows: incontinence due to flatus (score range from 0 to 7), incontinence due to liquid stools (score range from 0 to 3), frequency of bowel movements (score range from 0 to 5), clustering (score range from 0 to 11) and urgency (score range from 0 to 16). The severity of each item is calculated on a scale ranging from 0 to 42, with a score of 0-20 (no LARS), 21-29 (minor LARS) and 30-42 (major LARS).

Quality of life assessed using the EORTC Quality of Life questionnaire (QLQ)-C30 at 1 years after proctectomyAt 1 years after proctectomy

The European Organisation for Research and Treatment of Cancer (EORTC) developed and validated a 30-item core questionnaire (QLQ-C30) reflecting global QoL in cancer patients. QLQ-C30 comprises five functional scales, three symptom scales, a global health scale/ a quality of life scale, and six single items. All the scales and single item measures range in score from 0-100. A high score represents a higher level of functioning, a high quality of life, and a greater degree of symptoms.

Quality of life assessed using the EORTC Quality of Life questionnaire (QLQ)-CR29 at 1 years after proctectomyAt 1 years after proctectomy

QLQ-CR29 is developed by The European Organisation for Research and Treatment of Cancer (EORTC). It is a validated supplement to the QLQ-C30 specifically designed for assessment of quality of life in colorectal cancer patients. QLQ-CR29 consists of four functional scales and eighteen single items. All the scales range from 0-100. A high score represents a higher level of functioning and a greater degree of symptoms.

MSKCC BFI Score at 1 years after proctectomyAt 1 years after proctectomy

The Memorial Sloan-Kettering Cancer Centre Bowel Function Instrument (MSKCC BFI) score is a validated questionnaire for evaluation of bowel function after sphincter-preserving surgery. It comprises 18 items covering the frequency of various LARS symptoms and is divided into three sub-scales and four single items. It is scored on a 5-point Likert scale ranging from "always" to "never". The sub-scales scores are summarised as: A 6-item frequency sub-scale (6-30), a four-item dietary sub-scale (4-20), and a four-item urgency sub-scale (4-20). A global score can be calculated as the sum of the sub-scale scores. A total score (possible score range 18-90) can be calculated by adding all the item scores (sub-scale scores plus single item scores). A higher score indicates better bowel function.

Time for major LARS (≥30) returning to minor or no LARS (<30) after proctectomyWithin 1 years after proctectomy

LARS score is assessed every 6 months after proctectomy, and the time for major LARS (≥30) returning to minor or no LARS (\<30) is recorded. Low anterior resection syndrome (LARS) score is a tool consisting of five items, which are as follows: incontinence due to flatus (score range from 0 to 7), incontinence due to liquid stools (score range from 0 to 3), frequency of bowel movements (score range from 0 to 5), clustering (score range from 0 to 11) and urgency (score range from 0 to 16). The severity of each item is calculated on a scale ranging from 0 to 42, with a score of 0-20 (no LARS), 21-29 (minor LARS) and 30-42 (major LARS).

Other complications within 1 years after proctectomyWithin 1 years after proctectomy

Other complications is assessed by a professional doctor using Common Terminology Criteria for Adverse Events (CTCAE) classification.

Trial Locations

Locations (2)

the Sixth Affiliated Hospital, Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

the Fifth Affiliated Hospital, Sun Yat-Sen University

🇨🇳

Zhuhai, Guangdong, China

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