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

NCT ID: NCT01740947

Last Updated: 2018-11-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 485 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2017-03-31

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Standard treatment

Standard treatment for colorectal cancer

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Selective decontamination of the digestive tract (SDD) (colistin sulfate, tobramycin, amphotericin B)

Intervention Type: DRUG

SDD suspension contains per dose of 10 ml 100 mg colistin sulfate, 80 mg tobramycin and 500 mg amphotericin B

Interventions

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

Intervention Type: DRUG

Other Intervention Names

SDD

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dutch Digestive Diseases Foundation

OTHER

Sponsor Role: collaborator

H. Jaap Bonjer, PhD

OTHER

Sponsor Role: lead

Responsible Party

H. Jaap Bonjer, PhD

Professor of Surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

H.J. Bonjer, Md, PhD, FRCSC

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

G.S.A. Abis, MD, MSc

Role: STUDY_DIRECTOR

Amsterdam UMC, location VUmc

Locations

Slotervaart Ziekenhuis

Amsterdam, , Netherlands

VU University Medical Center

Amsterdam, , Netherlands

Kennemer Gasthuis

Haarlem, , Netherlands

Spaarne Ziekenhuis

Hoofddorp, , Netherlands

WestFries Gasthuis

Hoorn, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 30802304 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24814583 (View on PubMed)

Other Identifiers

2011-002211-28

Identifier Type: -

Identifier Source: org_study_id