Clinical trial NCT06214988: Selective Defunctioning Stoma in Low Anterior Resection for Rectal Cancer
Official title: SELective Defunctioning Stoma Approach in Low Anterior Resection for Rectal Cancer (SELSA): a Prospective Study With a Nested Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Keywords: anterior resection
defunctioning stoma
selective approach
Lead sponsor: Skane University Hospital
Sponsor class: OTHER
Collaborators: name: Umeå University
name: Lund University
name: Göteborg University
name: Ersta Hospital, Sweden
name: Copenhagen University Hospital at Herlev
name: Linkoeping University
name: Oslo University Hospital
name: Örebro University, Sweden
First posted: 2024-01-22
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Observational trial with nested randomized trial
Primary purpose: TREATMENT

Brief summary: The goal of this observational trial with a nested randomized controlled trial is to investigate a selective approach of defunctioning stoma in low anterior resection in rectal cancer patients. The primary outcome is a hybrid so-called textbook outcome; stoma-free survival at two years without major LARS, reflecting a functionally appropriate outcome after low anterior resection for rectal cancer. Secondary outcomes include anastomotic leakage, postoperative mortality, reinterventions, stoma-related complications, quality of life measures, LARS, and permanent stoma rate up to two years after index surgery.

Detailed description: Systematic use of defunctioning stoma after low anterior resection for rectal cancer has been shown to reduce symptomatic anastomotic leakage and associated interventions. However, accumulating data suggest that this comes at the price of worse bowel dysfunction, a higher rate of permanent stomas and kidney injury. We aim to study whether a selective strategy of defunctioning stoma use might lead to fewer adverse consequences, while still being safe for patients.

This is a multicentre international prospective trial including a non-blinded randomised clinical trial. All patients with a primary rectal cancer planned for low anterior resection with colorectal or coloanal anastomosis are eligible. Patients enter a prospective observational study, in which a randomised clinical trial is nested. Patients eligible for randomisation are aged below 80 years, have an American Society of Anesthesiologists' fitness grade I or II, have no unresected distant disease, and have a predicted lower risk of anastomotic leakage. Patients will be randomised 1:1 to either an experimental arm with no defunctioning stoma or to a control arm with a defunctioning stoma. The randomisation is computer-generated with a concealed sequence and stratified by participating hospital and radiotherapy use. The main outcome is the composite measure of 2-year stoma-free survival without major low anterior resection syndrome (LARS). Secondary outcomes include anastomotic leakage, postoperative mortality, reinterventions, stoma-related complications, quality of life measures, LARS, and permanent stoma rate up to two years after index surgery. To be able to state superiority of any study arm regarding the main outcome, with 90% statistical power and assuming 25% attrition, we aim to enrol 212 patients.

This study has been approved by Ethical Review Authority in Sweden (2023-04347-01) and seeks permission in Norway and Danmark, respectively. The results will be disseminated through patient associations, popular science, the broader medical community, and conventional scientific channels.

Eligibility criteria: Inclusion Criteria:

* Adult patients with rectal cancer planned for a low anterior resection with anastomosis by TME with any surgical approach

Additional inclusion criteria for randomised part of the study:

* Patients aged less than 80 years
* Patients with American Society of Anesthetists' (ASA) fitness grade I or II as determined by the anaesthesiologist or the surgeon
* Patients without clear radiological signs of distant disease before rectal cancer surgery (previous metastatic surgery is no exclusion criterion)
* Anastomotic leak risk score of 0-1
* Willingness to be randomised

Exclusion Criteria:

* Insufficient command of Swedish, Norwegian, Danish or English to understand questionnaires or consent
* Emergency rectal resection (tumour resection due to large bowel obstruction, perforation, etc)
* Pregnancy or breastfeeding Additional exclusion criteria for randomised part of the study
* Previous pelvic irradiation (due to e.g. gynaecological or urological cancer)
* Preoperative tumour perforation or pelvic sepsis
* Beyond TME surgery and/or concurrent resection of other organ
* Concurrent corticosteroid treatment (prednisone-equivalent dosage ≥10 mg daily)
* Planned postoperative chemotherapy
* Smoking not completely ceased four weeks before surgery
* Excessive alcohol consumption with social and medical consequences (as judged by the surgeon in charge) Intraoperative exclusion criteria for randomised part of the study

  -\>2 staple firings for rectal transection
* Intraoperative blood loss ≥250 ml for minimally invasive surgery
* Intraoperative blood loss ≥500 ml for open or converted surgery
* More than one intraabdominal anastomosis performed
* Incomplete doughnuts
* Air-leak test positive
* Any significant intraoperative adverse event at the discretion of the operating surgeon (e.g. ureterotomy, bowel or tumour perforation, major medical event - pulmonary embolism, cardiac arrhythmia) (Gawria, 2022)
* TME with anastomosis ultimately not done

Primary outcomes:
measure: textbook outcome; stoma-free survival at two years without major LARS
timeFrame: 2 year
Secondary outcomes:
measure: Anastomotic leakage
timeFrame: 1,3,12 and 24 months
measure: Complications
timeFrame: 1,3,12 and 24 months
measure: Length of hospital stay
timeFrame: until discharge within 90 days
measure: Postoperative mortality
timeFrame: 3 months
measure: Major Low Anterior Resection Syndrome
timeFrame: 12 and 24 months
measure: Quality of life by European Organization for Research and Treatment of Cancer- ColoRectal 29 (EORTC-CR29)
timeFrame: 12 and 24 months
measure: Quality of Recovery-15 Swedish (QoR15swe)
timeFrame: 1 month
measure: Adjuvant chemotherapy for high-risk patients
timeFrame: 12 months
measure: Renal function
timeFrame: 12 and 24 months
measure: Stay out of hospital
timeFrame: 24 months
measure: Stoma in situ
timeFrame: 24 months
measure: Recurrence (local and distant)
timeFrame: 36 and 60 months
measure: Overall survival
timeFrame: 36 and 60 months
measure: Quality of life by European Organization for Research and Treatment of Cancer- Cancer30 (EORTC-C30)
timeFrame: 12 and 24 months
Other outcomes:
Locations:
city: Malmö
country: Sweden
facility: Skåne University Hospital
Study officials:
affiliation: Skåne University Hospital, Lund University
name: Pamela Buchwald, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Umeå University Hospital, Umeå University Hospital
name: Martin Rutegård, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: