Clinical trial NCT01740947: Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
Official title: Perioperative Selective Decontamination of the Digestive Tract (SDD) in Elective Colorectal Cancer Patients: a Multicenter Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Colorectal Cancer
Keywords: Selective decontamination of the digestive tract
anastomotic leakage
colorectal cancer
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Dutch Digestive Diseases Foundation
First posted: 2012-12-04
Enrollment: 485
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: anastomotic leakage and/or abscess
timeFrame: 30 days postoperatively
Secondary outcomes:
measure: Disease free survival
timeFrame: 3 and 5 years after inclusion
Other outcomes:
measure: Other postoperative infectious complications
timeFrame: 30 days postoperatively
measure: Non-infectious complications
timeFrame: 30 days postoperatively
measure: In-hospital mortality
timeFrame: 30 days postoperatively
measure: Readmission rate
timeFrame: 5 years postoperatively
measure: Reoperation rate
timeFrame: 5 years postoperatively
measure: Duration of hospital stay
timeFrame: 30 days postoperatively
measure: Quality of life (quality adjusted life years)
timeFrame: 2 years postoperatively
measure: In hospital and out-of-hospital costs
timeFrame: 5 years postoperatively
Locations:
city: Amsterdam
country: Netherlands
facility: Slotervaart Ziekenhuis
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Hoorn
country: Netherlands
facility: WestFries Gasthuis
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: H.J. Bonjer, Md, PhD, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, location VUmc
name: G.S.A. Abis, MD, MSc
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.