Continuous Antibiotic Prophylaxis in Colorectal Surgery (Colo-Pro)

October 8, 2019 updated by: Andrew Kirby, University of Leeds

Colo-Pro Pilot: A Pilot Study to Compare Standard Single Dose Antibiotic Prophylaxis to Bolus-continuous Infusion Dosed Antibiotic Prophylaxis for the Prevention of Infections After Colorectal Surgery

We propose to randomise patients due to undergo colorectal surgery to standard antibiotic prophylaxis or an interventional antibiotic prophylaxis regimen and assess surgical wound infection rates. Standard antibiotic prophylaxis is a pre-operative injection of cefuroxime, repeated every 4 hours. The intervention regimen is a loading dose of cefuroxime followed by a continuous infusion of cefuroxime until the end of surgery. The intervention regimen dosing will be calculated using a patient's renal function and body weight. The intervention regimen will target a free serum drug concentration of 64mg/L. This serum level is 4x the MIC90 for colonising Enterobacteriaceae. The rational for this dosing regimen is summarised below. The primary objective of the study is to reduce by 50% the rate of surgical wound infections after colorectal surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An expert assessment is that fT>MIC is the measure most likely to be applicable to prophylaxis. But this measure is not achieved by standard prophylaxis regimens. Neither do clinical data suggest this target achieves optimal prophylaxis. Therefore there is an opportunity to optimise antibiotic prophylaxis dosing. As the exposure response-relationship (pharmacodynamic target) is unknown we could either complete a number of studies exploring different relationships, or compare standard treatment to a single regimen which included a number of exposure-response relationships. The two most common exposure-response relationships are the CMAX/MIC ratio and the fT>MIC. And it has been reported that killing, as opposed to inhibition used in MIC values, is optimised by achieving 4 times an MIC value. An antibiotic prophylaxis regimen which achieved drug concentrations of 4xMIC for the duration of surgery would therefore achieves a high CMAX/MIC ratio, high T>MIC, and optimise bacterial killing. Therefore, standard dose antibiotic prophylaxis will be compared against a PD target dosed antibiotic prophylaxis regimen. The PD target will be a free serum antibiotic concentration of 4xMIC90 for Enterobacteriaceae against cefuroxime. Continuous infusion of antibiotic prophylaxis will ensure there is continuous targeting of this drug level throughout the operation.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS1 3EX
        • Leeds Teaching Hospitals NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  • Undergoing colorectal surgery (incision, excision or anastomosis of the large bowel, including anastomosis of small to large bowel)
  • Age >18.
  • Expected duration of surgery > 2hours
  • Creatinine clearance > 40 ml/min
  • Cefuroxime/metronidazole are appropriate antibiotic prophylaxis regimens.
  • Patient capable of giving informed consent
  • Patients undergoing colorectal surgery plus additional surgery e.g. plastic surgery, urological surgery, gynaecological surgery.
  • If it is not possible to obtain intra-operative blood samples e.g. difficult vascular access, or pre-operative swabs e.g. anatomy makes it difficult to obtain, patients will be included and this information treated as missing data. Patients on antibiotic treatment for an existing infection (except SSIs) can be included in the study

Exclusion Criteria:

  • Unable to consent
  • Pregnancy
  • Expected duration of surgery <2hours
  • Creatinine clearance <40ml/min
  • Individual level microbiological advice for non cefuroxime based prophylaxis
  • Cephalosporin allergy
  • Penicillin allergy (hypersensitivity reaction only)
  • Coumarin (warfarin and acenocoumarol) treatment
  • Active blood borne virus infection e.g. HIV, hepatitis.
  • Seizure history
  • Concurrent use of probenecid
  • Current participation in a research project aimed at reducing SSIs
  • Antibiotics for treatment of a systemic Gram negative infection within 2 hours of initiation of surgery (Vancomycin, Teicoplanin, Daptomycin, Linezolid, Flucloxacillin. Nitrofurantoin and Clarithromycin would be permissible antibiotics without systemic Gram negative antibiotics).
  • A current diagnosis of a SSI at the time of study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard regimen
Cefuroxime 1.5grams pre-operatively Repeated every 4 hours
Drug: Cefuroxime 4 hourly bolus
Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.
Experimental: Interventional regimen
Cefuroxime continuous infusion targeting 64mg/l serum concentrations.
Drug: Cefuroxime 4 hourly bolus
Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With a Surgical Site Infection
Time Frame: Number of patients with a surgical site infection within 30 days of a colorectal surgical procedure.
Superficial and deep surgical site infections as defined by the CDC (Centre's for Disease Control) definitions of surgical site infections.
Number of patients with a surgical site infection within 30 days of a colorectal surgical procedure.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leeds

Investigators

  • Principal Investigator: Andrew Kirby, The University of Leeds

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2015

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

May 1, 2017

Study Registration Dates

First Submitted

May 13, 2015

First Submitted That Met QC Criteria

May 14, 2015

First Posted (Estimate)

May 15, 2015

Study Record Updates

Last Update Posted (Actual)

October 10, 2019

Last Update Submitted That Met QC Criteria

October 8, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MB15/130

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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