Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis? (SELECT)

Perioperative Selective Decontamination of the Digestive Tract (SDD) in Elective Colorectal Cancer Patients: a Multicenter Randomized Clinical Trial

The primary objectives of this randomized clinical trial are to evaluate if perioperative SDD can reduce clinical anastomotic leakage rate and its septic consequences as well as other infectious complications. By reduction of septic complications long-term oncological outcome might simultaneously improve.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Selective decontamination of the digestive tract (SDD) (colistin sulfate, tobramycin, amphotericin B)

Detailed Description

Rationale:

Infectious complications and especially anastomotic leakage severely impede the recuperation of patients following colorectal cancer surgery. When the normal gut barrier fails such as in anastomotic leakage, pathogenic microorganisms like Gram-negative bacteria enter the circulation and may cause severe sepsis which is associated with considerable mortality. Moreover, anastomotic leakage has a negative impact on colorectal cancer prognosis. Selective decontamination of the digestive tract (SDD) is a prophylaxis regimen that employs oral nonabsorbable antibiotics to eradicate pathogenic micro-organisms like Gram-negative bacteria.

Objective:

The primary objectives of this randomized clinical trial are to evaluate if perioperative SDD can reduce clinical anastomotic leakage rate and its septic consequences as well as other infectious complications. By reduction of septic complications long-term oncological outcome might simultaneously improve. Secondary objectives are a decline in reoperation rate, in-hospital mortality, readmission rate, duration of hospital stay and ICU admission, non-infectious complications, improvement of quality of life and reduction of costs.

Study design:

A randomised multicenter clinical trial comparing perioperative SDD in addition to standard antibiotic prophylaxis with standard antibiotic prophylaxis alone in patients with colorectal cancer who undergo elective surgical resection with curative intent.

Study population:

Patients 18 years or older are eligible for inclusion when they are diagnosed with colon or rectal cancer without signs of distant metastases. Patients may be scheduled for either laparoscopic or open resection with curative intent, including construction of an anastomosis (either with or without diverting stoma). Patients are not eligible for inclusion in case of concomitant metastases or acute obstruction.

Intervention:

Patients are randomly allocated for either perioperative SDD (intervention group) including standard antibiotic prophylaxis or standard treatment (including standard antibiotic prophylaxis alone) (control group). The solution containing SDD is orally taken 4 times daily, starting 3 days before surgery and continued until normal bowel passage or at least 3 days after surgery. Both groups receive a single preoperative intravenous dose of 1000 mg Cefazoline and 500 mg Metronidazole, which is the current standard antibiotic prophylaxis.

Main study parameters/endpoints:

The main study parameter is anastomotic leakage. The research hypothesis refers to an estimated decrease in anastomotic leakage rate in the SDD treated group (from 9% to 4%). As anastomotic leakage has been shown unfavourable forlong term oncological outcome, we presume an improvement in disease free survival, which serves as important secondary endpoint.

• Study Type: Interventional
• Enrollment (Actual): 485
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VU University Medical Center
  • Amsterdam, Netherlands
    • Slotervaart Ziekenhuis
  • Haarlem, Netherlands
    • Kennemer Gasthuis
  • Hoofddorp, Netherlands
    • Spaarne Ziekenhuis
  • Hoorn, Netherlands
    • Westfries Gasthuis

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Elective colon and rectal cancer surgery with primary anastomosis
• Or elective colorectal surgery for suspected carcinoma
• No evidence of distant metastases (preoperative CT-abdomen and X-thorax or CTthorax)
• Procedure either with or without diverting stoma
• Both laparoscopic and open surgery
• Informed consent
• Aged 18 years or older

Exclusion Criteria:

• Previous colorectal malignancy
• Current malignancy which is now undergoing treatment
• Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• Previous surgery for diverticular disease
• Performance status ASA 4 or higher (American Society for Anaesthesiologists)
• Expected adverse reactions/allergies for study medication
• Prednisone use > 5 mg per day
• Familial adenomatous polyposis coli (FAP; Lynch syndrome), Hereditary Non Polyposis Colorectal Cancer (HNPCC)
• Mental disorder/unable to give informed consent
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment; Standard treatment for colorectal cancer
Experimental: Selective decontamination of the digestive tract (SDD); Standard treatment + SDD perioperatively 4 times daily 10 ml of SDD suspension, consisting of 100mg colistin sulfate, 80mg tobramycin and 500mg of amphotericin B. SDD treatment starts 3 days before surgery and is continued until at least 3 days postoperatively.	Drug: Selective decontamination of the digestive tract (SDD) (colistin sulfate, tobramycin, amphotericin B); SDD suspension contains per dose of 10 ml 100 mg colistin sulfate, 80 mg tobramycin and 500 mg amphotericin B; Other Names: SDD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anastomotic leakage and/or abscess	clinical and/or radiological evidence of anastomotic dehiscence requiring surgical or radiological (re)intervention.	30 days postoperatively

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	3 and 5 years after inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other postoperative infectious complications	pneumonia, urinary tract infections, surgical site infections, wound dehiscence, (remote) intraabdominal abscess	30 days postoperatively
Non-infectious complications	cardiac failure, cerebrovascular events, deep venous thrombosis	30 days postoperatively
In-hospital mortality		30 days postoperatively
Readmission rate		5 years postoperatively
Reoperation rate		5 years postoperatively
Duration of hospital stay		30 days postoperatively
Quality of life (quality adjusted life years)		2 years postoperatively
In hospital and out-of-hospital costs		5 years postoperatively

Collaborators and Investigators

• Sponsor: H. Jaap Bonjer, PhD
• Collaborators: Dutch Digestive Diseases Foundation
• Investigators: Principal Investigator: H.J. Bonjer, Md, PhD, FRCSC, Amsterdam Umc, Location Vumc; Study Director: G.S.A. Abis, MD, MSc, Amsterdam Umc, Location Vumc

Publications and helpful links

General Publications

• Abis GSA, Stockmann HBAC, Bonjer HJ, van Veenendaal N, van Doorn-Schepens MLM, Budding AE, Wilschut JA, van Egmond M, Oosterling SJ; SELECT trial study group. Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial). Br J Surg. 2019 Mar;106(4):355-363. doi: 10.1002/bjs.11117. Epub 2019 Feb 25.
• Abis GS, Oosterling SJ, Stockmann HB, van der Bij GJ, van Egmond M, Vandenbroucke-Grauls CM, Bonjer HJ. Perioperative selective decontamination of the digestive tract and standard antibiotic prophylaxis versus standard antibiotic prophylaxis alone in elective colorectal cancer patients. Dan Med J. 2014 Apr;61(4):A4695.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: November 27, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): November 9, 2018
• Last Update Submitted That Met QC Criteria: November 7, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: colorectal cancer; anastomotic leakage; Selective decontamination of the digestive tract
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Tobramycin; Colistin; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: 2011-002211-28