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Continuous Antibiotic Prophylaxis in Colorectal Surgery (Colo-Pro)

Primary Purpose

Surgical Site Infection

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Cefuroxime 4 hourly bolus
Sponsored by
University of Leeds
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Surgical Site Infection focused on measuring Antibiotic, prophylaxis, surgical site infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Leeds Teaching Hospitals NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard regimen

Interventional regimen

Arm Description

Cefuroxime 1.5grams pre-operatively Repeated every 4 hours

Cefuroxime continuous infusion targeting 64mg/l serum concentrations.

Outcomes

Primary Outcome Measures

Number of Patients With a Surgical Site Infection
Superficial and deep surgical site infections as defined by the CDC (Centre's for Disease Control) definitions of surgical site infections.

Secondary Outcome Measures

Full Information

First Posted
May 13, 2015
Last Updated
October 8, 2019
Sponsor
University of Leeds
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1. Study Identification

Unique Protocol Identification Number
NCT02445859
Brief Title
Continuous Antibiotic Prophylaxis in Colorectal Surgery
Acronym
Colo-Pro
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Leeds

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Site Infection
Keywords
Antibiotic, prophylaxis, surgical site infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard regimen
Arm Type
Active Comparator
Arm Description
Cefuroxime 1.5grams pre-operatively Repeated every 4 hours
Arm Title
Interventional regimen
Arm Type
Experimental
Arm Description
Cefuroxime continuous infusion targeting 64mg/l serum concentrations.
Intervention Type
Drug
Intervention Name(s)
Cefuroxime 4 hourly bolus
Intervention Description
Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.
Primary Outcome Measure Information:
Title
Number of Patients With a Surgical Site Infection
Description
Superficial and deep surgical site infections as defined by the CDC (Centre's for Disease Control) definitions of surgical site infections.
Time Frame
Number of patients with a surgical site infection within 30 days of a colorectal surgical procedure.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Kirby
Organizational Affiliation
The University of Leeds
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leeds Teaching Hospitals NHS Trust
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS1 3EX
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30519893
Citation
Kirby A, Asin-Prieto E, Burns FA, Ewin D, Fatania K, Kailavasan M, Nisar S, Pericleous A, Troconiz IF, Burke D. Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery. Eur J Clin Microbiol Infect Dis. 2019 Feb;38(2):357-363. doi: 10.1007/s10096-018-3435-z. Epub 2018 Dec 5.
Results Reference
derived

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Continuous Antibiotic Prophylaxis in Colorectal Surgery

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