Somatostatin Plus Clear Liquid Diet Versus Diverting Stoma in Patients With Rectal Cancer Undergoing Ultra-Low Anterior Resection

Official title

A Multicenter, Randomized Clinical Study of Somatostatin Plus Clear Liquid Diet Versus Diverting Stoma in Patients With Low and Mid Rectal Cancer Undergoing Ultra-Low Anterior Resection

Overview

The goal of this clinical trial is to learn if somatostatin plus a clear liquid diet can help prevent severe leakage after rectal cancer surgery in adults with low or mid rectal cancer who are scheduled to have ultra-low anterior resection. These patients have a higher risk of leakage where the bowel is joined together after surgery. The main questions it aims to answer are: Does somatostatin plus a clear liquid diet prevent severe leakage within 1 month after surgery about as well as a prophylactic diverting stoma? What medical problems, bowel function problems, recovery outcomes, and quality of life outcomes do participants have after surgery and during follow-up? Researchers will compare somatostatin plus a clear liquid diet without a diverting stoma to prophylactic diverting stoma to see if the somatostatin plus clear liquid diet regimen can provide similar protection against severe leakage while reducing the need for stoma creation. Participants will: Have rectal cancer surgery with the bowel joined very close to the anus Be randomly assigned to receive either somatostatin plus a clear liquid diet for 7 days after surgery without a diverting stoma, or a prophylactic diverting stoma Have follow-up assessments of leakage, postoperative complications, bowel function, recovery quality, and quality of life Complete follow-up visits or assessments for up to 3 years after surgery

Detailed description

This is a multicenter, open-label, randomized clinical trial evaluating a postoperative no-stoma management strategy in adults with low or mid rectal cancer undergoing ultra-low anterior resection. Patients undergoing ultra-low colorectal or coloanal anastomosis are at increased risk of anastomotic leakage. A prophylactic diverting stoma is commonly used to reduce the clinical consequences of leakage, but stoma creation may also lead to stoma-related complications, delayed stoma closure, additional surgery, and impaired quality of life.

The study evaluates whether a 7-day postoperative regimen of somatostatin plus a clear liquid diet can serve as an alternative strategy to reduce intestinal contents passing through the anastomosis during the early postoperative period. Somatostatin is used to reduce gastrointestinal secretions, and a clear liquid diet is used to limit solid residue in the digestive tract. The investigational strategy is compared with prophylactic diverting stoma, which is commonly used in patients considered to be at high risk of leakage after low rectal surgery.

Eligible participants will be randomly assigned in a 1:1 ratio to one of two treatment strategies after ultra-low anterior resection. Participants in the experimental group will not undergo prophylactic stoma creation and will receive somatostatin plus a clear liquid diet for 7 days after surgery. Participants in the control group will undergo prophylactic diverting stoma and receive standard postoperative care. Both groups will receive routine perioperative management according to clinical practice at the participating centers.

The primary clinical focus is severe anastomotic leakage within 1 month after surgery, defined as leakage requiring reoperation. The study will also assess postoperative complications, bowel function, quality of recovery, quality of life, and longer-term functional outcomes during follow-up. Participants will be followed for up to 3 years after surgery.

This trial is intended to determine whether somatostatin plus a clear liquid diet without prophylactic stoma can provide similar protection against severe anastomotic leakage compared with prophylactic diverting stoma, while reducing the need for stoma creation and its related burden.

Interventions

• Drug Somatostatin
  Participants in the experimental arm will receive somatostatin 3 mg diluted in 50 mL of 0.9% sodium chloride by intravenous infusion pump at 4.1 mL/hour every 12 hours for 7 days after surgery, as part of the postoperative no-stoma management strategy.
• Other Clear Liquid Diet
  Participants in the experimental arm will receive a clear liquid diet after recovery of bowel gas passage, as part of the 7-day postoperative no-stoma management strategy. Parenteral nutrition may be provided according to clinical needs.
• Procedure Prophylactic Diverting Stoma
  Participants in the control arm will undergo prophylactic diverting stoma creation during ultra-low anterior resection and will receive standard postoperative care. Somatostatin will not be routinely used unless clinically necessary.

Primary outcome measures

• Grade C Anastomotic Leakage Within 1 Month After Surgery [Time frame: Within 1 month after surgery]

Secondary outcome measures (3)

• Postoperative Complication Severity Within 1 Month After Surgery [Time frame: Within 1 month after surgery]
• Low Anterior Resection Syndrome Score Within 1 Month After Surgery [Time frame: 7 days, 14 days, and 1 month after surgery]
• Quality of Recovery Score Within 1 Month After Surgery [Time frame: 7 days, 14 days, and 1 month after surgery]

Eligibility criteria

Inclusion criteria

• Adults aged 18 to 75 years
• Patients with stage I to III rectal malignancy who are scheduled to undergo low anterior resection at a participating gastrointestinal surgery center
• The lower edge of the tumor is 8 cm or less from the dentate line, or 10 cm or less from the anal verge, based on preoperative colonoscopy, imaging, or digital rectal examination
• The planned anastomosis is expected to be 2 cm or less from the dentate line, or 4 cm or less from the anal verge
• Patients have two or more risk factors for anastomotic leakage as assessed by the study team
• American Society of Anesthesiologists physical status classification is grade 3 or lower
• Body mass index is less than 30 kg/m²
• The patient, or the patient's legally authorized representative, is willing and able to provide written informed consent

Exclusion criteria

• Has another colorectal malignant tumor at the same time
• The final anastomosis after surgery is more than 2 cm from the dentate line, or more than 4 cm from the anal verge
• Has metastatic disease before surgery
• Is pregnant
• Has a mental illness or addictive disorder that would prevent participation in the clinical trial
• Requires emergency surgery
• Has inflammatory bowel disease
• Is allergic to somatostatin or is unable to tolerate somatostatin
• For participants assigned to the no-stoma group, the surgeon decides that a stoma is required
• Has received neoadjuvant drug therapy less than 2 weeks before surgery, or radiotherapy less than 8 weeks before surgery
• Has any other condition that makes it impossible to follow the study protocol

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Ezhou Central Hospital — Ezhou
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• Wuhan No. 6 Hospital — Wuhan

Publications

• Kang CY, Halabi WJ, Chaudhry OO, Nguyen V, Pigazzi A, Carmichael JC, Mills S, Stamos MJ. Risk factors for anastomotic leakage after anterior resection for rectal cancer. JAMA Surg. 2013 Jan;148(1):65-71. doi: 10.1001/2013.jamasurg.2. PMID 22986932
• Stevens P, Foulkes RE, Hartford-Beynon JS, Delicata RJ. Systematic review and meta-analysis of the role of somatostatin and its analogues in the treatment of enterocutaneous fistula. Eur J Gastroenterol Hepatol. 2011 Oct;23(10):912-22. doi: 10.1097/MEG.0b013e32834a345d. PMID 21814141
• Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013 Jun;118(6):1332-40. doi: 10.1097/ALN.0b013e318289b84b. PMID 23411725
• Emmertsen KJ, Laurberg S. Low anterior resection syndrome score: development and validation of a symptom-based scoring system for bowel dysfunction after low anterior resection for rectal cancer. Ann Surg. 2012 May;255(5):922-8. doi: 10.1097/SLA.0b013e31824f1c21. PMID 22504191
• Kulu Y, Ulrich A, Bruckner T, Contin P, Welsch T, Rahbari NN, Buchler MW, Weitz J; International Study Group of Rectal Cancer. Validation of the International Study Group of Rectal Cancer definition and severity grading of anastomotic leakage. Surgery. 2013 Jun;153(6):753-61. doi: 10.1016/j.surg.2013.02.007. Epub 2013 Apr 25. PMID 23623834
• Rahbari NN, Weitz J, Hohenberger W, Heald RJ, Moran B, Ulrich A, Holm T, Wong WD, Tiret E, Moriya Y, Laurberg S, den Dulk M, van de Velde C, Buchler MW. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery. 2010 Mar;147(3):339-51. doi: 10.1016/j.surg.2009.10.012. Epub 2009 Dec 11. PMID 20004450
• Matthiessen P, Hallbook O, Rutegard J, Simert G, Sjodahl R. Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial. Ann Surg. 2007 Aug;246(2):207-14. doi: 10.1097/SLA.0b013e3180603024. PMID 17667498

Identifiers

NCT: NCT07605611 · TJ-IRB202601038

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗