Mechanical Bowel Prep Randomized Study

Is Mechanical Bowel Preparation Necessary to Reduce Surgical Site Infection Following Colon Surgery: A Randomized Controlled Trial

Following colon surgery, surgical site infection (SSI) is the most common complication and leads to longer recovery time for patients and increased health care costs. Currently, there is high quality evidence to show that the combination of intravenous antibiotics (IVA), mechanical bowel preparation (MBP) and oral antibiotics (OA) is the most effective bowel preparation to reduce SSI. However, there are no studies comparing IVA+MBP+OA and IVA+OA. This is an important question because if IVA+OA works the same as IVA+MBP+OA, then MBP may be safely omitted as part of the bowel preparation to reduce SSI and patients would avoid the side effects of MBP prior to their surgery. Therefore, the objective is to perform a trial to determine if IVA+OA works the same as IVA+MBP+OA to reduce SSI following colon surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Surgery
• Intervention / Treatment: Other: IVA+OA versus IVA+MBP+OA

Detailed Description

Background: Colon surgery includes surgery for colon cancer, inflammatory bowel disease and other benign disease such as diverticulitis. In Canada, approximately 21,000 colon surgeries are performed annually. Following colon surgery, the most common complication is surgical site infection (SSI) and rates of up to 25% have been reported. The high volume of colon cancer surgery, coupled with high rates of SSI lead to considerably worse health care outcomes for patients including increased recovery time, length of stay and readmission. Currently, several different bowel preparations to reduce SSI are being used in Canada and there is significant practice variation due to lack of RCTs and conflicting practice guidelines. More recently, several large observational studies and a network meta-analysis have shown that a combination of intravenous antibiotics, mechanical bowel preparation and oral antibiotics (IVA+MBP+OA) is superior to IVA+MBP and IVA alone. Interestingly, these studies also showed that SSI rates for IVA+OA are comparable to IVA+MBP+OA. These data provide a strong rationale to conduct a RCT comparing IVA+OA versus IVA+MBP+OA to determine if MBP is a necessary part of the bowel preparation or if MBP can be safely omitted and the side effects of MBP avoided.

Objectives: Therefore, the objectives are to conduct a multi-centre, parallel, two arm, non-inferiority RCT comparing IVA+MBP+OA versus IVA+OA to reduce SSI following colon surgery.

Methods: The inclusion criteria are any patient (i) undergoing elective colon surgery, (ii) over the age of 18 years and (3) provides informed consent. Eligible patients at 4 centres across Canada will be randomized to one of two groups: IVA+OA+MBP or IVA+OA. The primary outcome for the trial is the overall rate of SSI at 30 days following surgery. Assuming an overall SSI rate of 7% with IVA+MBP+OA and a non-inferiority margin of 4.0%, 1062 patients will be required with a one sided alpha of 0.05 and a power of 80%. This non-inferiority margin was unanimously accepted as clinically meaningful by all of the Site Leads at participating centres. Primary analyses will be performed per-protocol in patients who received treatment as allocated and underwent colon surgery. Overall SSI rates at 30 days following surgery will be compared using a general linear model and non-inferiority will be declared if the upper limit of the one sided 95% confidence interval of the absolute risk difference of overall SSI following surgery does not include 4.0%.

Relevance: This trial will be highly relevant to both patients and physicians as the results will provide definitive, high quality, patient-centred evidence about whether MBP is a necessary part of the optimal bowel preparation to reduce SSI and improve both patient experience and outcomes. These results will have significant potential to change practice in Canada and world-wide.

• Study Type: Interventional
• Enrollment (Estimated): 1062
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• undergoing elective colon surgery for benign or malignant disease
• over the age of 18 years
• provides informed consent.

Exclusion Criteria:

• known anaphylaxis to neomycin or metronidazole
• pregnancy or lactation
• chronic renal failure (serum creatinine > 220 umol/L).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: IV and Oral antibiotics (IVA+OA); Patients will receive cefazolin 2g IV and metronidazole 500 mg IV administered by the anesthesiologist within 60 minutes prior to the skin incision on the day of surgery. Standardized re-dosing of cefazolin 2g IV will occur every 4 hours and metronidazole 500 mg IV will occur every 8 hours during the surgical procedure. Following surgery, no further IVA will be given for SSI prophylaxis. In addition, patients will self-administer 1g neomycin and 1g metronidazole orally at 1500, 1700 and 2300 hours the day before surgery. Following this, they will not receive any further OAs for SSI prophylaxis.	Other: IVA+OA versus IVA+MBP+OA; Non-inferiority RCT comparing IVA+OA+MBP vs IVA+OA to reduce surgical site infection following colon surgery
Active Comparator: Group B: IV antibiotics, MBP and oral antibiotics (IVA+MBP+OA); Patients will receive IVA and OA per Group A. In addition, patients will stay on clear fluids and self-administer a 2L polyethylene glycol MBP orally, between 1500 and 2300 hours on the day before surgery.	Other: IVA+OA versus IVA+MBP+OA; Non-inferiority RCT comparing IVA+OA+MBP vs IVA+OA to reduce surgical site infection following colon surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Site Infection Rate	Rate of overall surgical site infection	30 days following date of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient tolerability of the bowel preparation	Validated 9-item questionnaire entitled: "Mayo Clinic Bowel Prep Tolerability Questionnaire" (Scale 1-4; lower score = better outcome)	5 minutes (completed in pre-operative holding area on the day of surgery)
Length of stay	length of stay in hospital following colorectal procedure	2-7 days
30-day ER rate	emergency room visit rate to any hospital within 30 days of surgery	30 days
30-day readmission rate	readmission rate to any hospital within 30 days of surgery	30 days

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Surgical Site Infection; Randomized Controlled Trial; Mechanical Bowel Preparation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Wound Infection; Surgical Wound Infection
• Other Study ID Numbers: PJT-165836

Drug and device information, study documents

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