REsults of LOw Anterior Resections With or Without Preventive Stoma in Nonemergency Department (RELOAD)

Results of Anastomotic Leak After Low Anterior Resection With or Without Preventive Stoma for Rectal Cancer in Low-risk Patients in Nonemergency Departments (RELOAD): Protocol of Multicenter Randomized Controlled Non-inferiority Trial

The purpose of this multicenter randomized non-inferiority trial is to evaluate the safety of low anterior resection for rectal cancer performed with versus without a diverting stoma in patients with a low predicted risk of colorectal anastomotic leakage.

The primary objective is to determine whether the rate of anastomotic leakage within 30 days after surgery in the no-stoma group is non-inferior to that in the diverting stoma group.

The secondary objectives include comparison between groups regarding: Stoma rate at 1 year after surgery; Quality of life at 30 days and 1 year (EORTC QLQ-C30, EORTC QLQ-CR29, and LARS score); Short-term postoperative outcomes, including postoperative day metrics, length of hospital stay, and complications graded according to the Clavien-Dindo classification; Reoperation rates within 30 days and 1 year.

Participants will include adult patients with mid- or low-rectal adenocarcinoma who are scheduled for radical minimally invasive total mesorectal excision and have a predicted risk of anastomotic leakage <10% according to the study risk model.

Study Overview

• Status: Recruiting
• Conditions: Local Advanced Rectal Cancer; Rectal Cancer Surgery; Low Rectal Cancer; Middle Rectal Cancer; TME
• Intervention / Treatment: Procedure: Without a preventive stoma; Procedure: With a preventive stoma

Detailed Description

This study is a multicenter randomized controlled non-inferiority trial evaluating the safety of omitting routine diverting stoma formation in low-risk patients undergoing total mesorectal excision (TME) for mid- and low-rectal cancer.

Patients with a predicted risk of colorectal anastomotic leakage (AL) ≤10% will be enrolled across 7 accredited centers. Local Ethics Committee approval has been obtained at each site. The protocol follows the SPIRIT 2025 recommendations.

After informed consent, patients will be randomized 1:1 to "with preventive stoma" and "without preventive stoma". Stratified block randomization (block sizes 2, 4, or 6) will be used, stratified by center and sex. Allocation will be computer-generated (R software). No blinding will be performed. Cross-over to stoma formation in the no-stoma group is permitted in case of intraoperative safety concerns.

All patients will undergo minimally invasive TME according to oncological principles (sharp dissection within embryological planes, adequate vascular control, stapled tension-free colorectal anastomosis).

In the stoma group, a diverting ileostomy or colostomy will be created. Closure is planned ≥2-3 months postoperatively if clinically appropriate.

Postoperative care follows institutional standards. Complications will be graded according to the Clavien-Dindo classification. Patients will be followed for 1 year with clinical visits (or telephone follow-up) at 30 days and every 3 months. Imaging and colonoscopy will be performed according to clinical guidelines. Quality-of-life assessments and LARS score will be obtained at 30 days and 1 year.

Risk Prediction Model. To include the patient in the study, the risk of anastomotic leaks will be assessed on the AFOR scale. If the value is 0-1 (6-10%), the patient will be invited to participate.

Sample Size and Statistical Analysis. Assuming a baseline AL rate of 15% in the stoma group, a non-inferiority margin of 10%, one-sided α=2.5%, 80% power, and 10% dropout rate, 442 patients (221 per group) are required. The primary analysis will follow the intention-to-treat (ITT) principle. A binomial logistic regression model will estimate risk difference with 95% confidence intervals using clustered robust standard errors by center. Non-inferiority will be concluded if the upper bound of the confidence interval does not cross the predefined margin. Sensitivity analyses will include per-protocol and instrumental variable approaches. Missing data for secondary outcomes will be handled using multiple imputation (MCAR assumption).

Interim Safety Analysis. A safety analysis will be conducted after enrollment of 50 patients per group. If unacceptable differences in AL rates are observed, early termination may be considered.

• Study Type: Interventional
• Enrollment (Estimated): 442
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vladislava S Goncharova, Ms.; Phone Number: +7 900 468 9026; Email: vladislava.26@mail.ru
• Study Contact Backup: Name: Nikita N Burlov, Dr.; Phone Number: +79819430019; Email: dikefsound@gmail.com

Study Locations

• Russia
  • Moscow, Russia, 143423
    • Recruiting
    • Moscow City Oncology Hospital No. 62 of the Moscow Department of Health
    • Contact: Ilya Chernikovsky; Phone Number: +79216576756; Email: odindra@mail.ru
  • Moscow, Russia
    • Recruiting
    • Central Clinical Hospital of the Administrative Directorate of the President of the Russian Federation
    • Contact: Artem Goncharov; Phone Number: +79990112121; Email: goncharovartemleo@gmail.com
  • Moscow, Russia
    • Recruiting
    • State Budgetary Institution of Healthcare of the city of Moscow "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of the Department of Healthcare of the City of Moscow"
    • Contact: Vischeslav Aliev; Phone Number: +79990112121; Email: afandiali76@gmail.com
  • Nizhny Novgorod, Russia
    • Recruiting
    • State Autonomous Healthcare Institution of Nizhny Novgorod Region "Research Institute of Clinical Oncology "Nizhny Novgorod Regional Clinical Oncology Dispensary""
    • Contact: Gleb Khrykov; Phone Number: +79990112121; Email: ghrykov@mail.ru
  • Saint Petersburg, Russia
    • Recruiting
    • Leningrad Regional Clinical Hospital
    • Contact: Alexey Smirnov; Phone Number: +79990112121; Email: oncsmirnov@yandex.ru
  • Ufa, Russia
    • Recruiting
    • Republican clinical oncological center
    • Contact: Rustem Ayupov; Phone Number: +79990112121; Email: ru2003@bk.ru
  • Yekaterinburg, Russia
    • Recruiting
    • Sverdlovsk Regional Oncological Center
    • Contact: Nikolay Makhotin; Phone Number: +79990112121; Email: n.v.mahotin@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18 years;
• Primary rectal cancer staged as cT1-4aN0-3M0 (or ycT0-4aN0-2M0);
• Histologically confirmed rectal adenocarcinoma based on endoscopic biopsy;
• Tumor located ≤12 cm from the dentate line (based on endoscopy, digital rectal examination, and/or pelvic MRI);
• Planned radical minimally invasive (laparoscopic/robot-assisted) intervention with TME and formation of primary colorectal/colonanal anastomosis;
• Adequate hematologic function: hemoglobin ≥100 g/L, leukocytes >4 × 10^9/L, platelets >100 × 10^9/L;
• Adequate renal function: serum creatinine <150 µmol/L;
• Adequate hepatic function: AST/ALT <100 U/L;
• Predicted risk of anastomotic leakage ≤10% (AFOR 0-1).

Exclusion Criteria:

• Age ≥80 years;
• Presence of a pre-existing diverting ileostomy or colostomy;
• Peritumoral abscess or tumor perforation;
• Distant metastases (M1) identified preoperatively and/or intraoperatively;
• Synchronous or metachronous malignancy;
• Prior pelvic irradiation for another condition (e.g., cervical or prostate cancer);
• Evidence of malnutrition (serum albumin <34 g/L);
• Severe uncontrolled comorbid conditions (e.g., acute myocardial infarction, uncontrolled hypertension, decompensated heart failure, immunosuppression, systemic corticosteroid therapy, severe chronic obstructive pulmonary disease, chronic kidney disease stage 4-5), type 1 or type 2 diabetes mellitus, or psychiatric/neurological disorders impairing the ability to provide informed consent;
• Tumor invasion into adjacent structures or organs (cT4b) identified preoperatively and/or intraoperatively;
• Predicted risk of anastomotic leakage >10% (AFOR 2-6).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Without a preventive stoma; In the no-stoma group, a diverting stoma will not be created provided there are no intraoperative complications and surgical safety principles are maintained. If intraoperative findings suggest a high risk of anastomotic leakage such as a positive air leak test of the colorectal anastomosis, bowel perforation, use of three or more linear stapler cartridges, blood loss >300 mL, impaired bowel wall perfusion, or tension at the anastomotic site and/or if patient safety is deemed at risk, a diverting stoma may be created at the surgeon's discretion (cross-over).	Procedure: Without a preventive stoma; At the conclusion of total mesorectal excision (TME), a diverting ileostomy or transverse colostomy will be created at the discretion of the operating surgeon. The pelvic peritoneum over the anastomotic site will be closed, and a pelvic drain will be placed (the type of drain will be determined by the operating surgeon).
Active Comparator: With a preventive stoma; In the stoma group, a diverting ileostomy or colostomy will be created at the end of the surgical procedure in the right or left lateral abdominal wall, according to the technique routinely used at each participating center. Stoma closure will be planned according to standard practice (no earlier than 2-3 months after surgery), provided there are no contraindications.	Procedure: With a preventive stoma; The operating surgeon will follow the standard practice adopted at the respective center and will create either a diverting ileostomy or transverse colostomy at their discretion. The pelvic peritoneum will not be closed. Placement of a percutaneous pelvic drain adjacent to the anastomotic site is mandatory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colorectal anastomotic leak	If anastomotic leakage is suspected in the postoperative period defined by worsening abdominal pain (>5-point increase on the Visual Analog Scale), signs of peritonitis, drain output containing fibrin or intestinal content, or radiologic findings suggestive of leakage on contrast-enhanced CT of the abdomen and pelvis (with or without proctography) and/or findings at diagnostic laparoscopy. Diagnostic and/or therapeutic measures will be undertaken to confirm or rule out the complication.	30 days after main surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	total days in hospital	until discharge within 90 days
Postoperative complications	Postoperative complications will be classified according to the Clavien-Dindo classification	30 days after main surgery
Reoperation rate	During a clinic visit or by telephone interview	30 days and 1 year after main surgery
Stoma rate	During a clinic visit or by telephone interview	1 year after main surgery
Hospital readmissions	The frequency of repeated admissions to this or other hospitals after the patient's discharge	30 days after main surgery
Quality of life by European Organization for Research and Treatment of Cancer-Cancer30 (EORTC-C30)	EORTC-C30 domain scores in scales 0-100 points, a high score for the global health status /quality of life represents a high quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	30 days and 1 year after surgery
Quality of life by European Organization for Research and Treatment of Cancer-ColoRectal 29 (EORTC-CR29)	EORTC-CR29 domain scores in scales 0-100 points, a high score for the global health status /quality of life represents a high quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	30 days and 1 year after surgery
Low Anterior Resection Syndrome (LARS)	At 1 year, assessment of Low Anterior Resection Syndrome (LARS) will be performed during a clinic visit or by telephone interview.	1 year after main surgery

Collaborators and Investigators

• Sponsor: ANO Scientific and Practical Club for the Development of Modern Medical Technologies

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2026
• Primary Completion (Estimated): June 10, 2027
• Study Completion (Estimated): June 10, 2027

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: randomized trial; anastomotic leak; rectal cancer; low-risk patients; preventive stoma
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Pathological Conditions, Signs and Symptoms; Rectal Neoplasms; Anastomotic Leak
• Other Study ID Numbers: 07/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No