Continuous Antibiotic Prophylaxis in Colorectal Surgery

NCT02445859 | Completed Phase 2 Results DMC

• 1 other identifier: MB15/130
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Surgical Site Infection

Keywords

Antibiotic; prophylaxis; surgical site infection

Outcome Measures

Primary Outcomes (1)

• 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.

  Number of patients with a surgical site infection within 30 days of a colorectal surgical procedure.

Study Arms (2)

Standard regimen

ACTIVE COMPARATOR

Cefuroxime 1.5grams pre-operatively Repeated every 4 hours

Drug: Cefuroxime 4 hourly bolus

Interventional regimen

EXPERIMENTAL

Cefuroxime continuous infusion targeting 64mg/l serum concentrations.

Drug: Cefuroxime 4 hourly bolus

Interventions

Cefuroxime 4 hourly bolus DRUG

Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.

Interventional regimen; Standard regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS1 3EX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30519893 DERIVED

MeSH Terms

Conditions

Surgical Wound Infection

Condition Hierarchy (Ancestors)

Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

These patients are expected to have multiple adverse events. We only formally collected all serious adverse events, plus specific events e.g. C.difficile. As a pilot trial we have learned about the collection of adverse events in this patient group.

Results Point of Contact

• Title: Andrew Kirby
• Organization: The Universit yof Leeds

a.kirby@leeds.ac.uk

0044 113 3923989

Study Officials

• Andrew Kirby

  The University of Leeds

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate clinical professor

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 15, 2015
• Study Start: August 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: October 10, 2019
• Results First Posted: September 12, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)