Clinical trial NCT05609240: Colo-Pro_2: Bolus-continuous Infusion Cefuroxime Prophylaxis for the Prevention of Infections After Colorectal Surgery
Official title: Colo-Pro_2: A Feasibility Randomised Controlled Double Blind Trial to Compare Standard Bolus Dosed Cefuroxime Prophylaxis to Bolus-continuous Infusion Dosed Cefuroxime Prophylaxis for the Prevention of Infections After Colorectal Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Antibiotic Prophylaxis
Colorectal Surgery
Keywords: Cefuroxime
Antibiotic
Colorectal
Prophylaxis
Surgery
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: University of Birmingham
name: Aneurin Bevan University Health Board
First posted: 2022-11-08
Enrollment: 180
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: After a surgical operation patients may have an infection in the operation wound, the bladder, kidneys or lungs. To stop these infections patients are given a dose of antibiotic before their operation. Unfortunately, the amount of antibiotic available to fight infections falls throughout an operation, being removed from the body by the kidneys. Therefore, antibiotic levels may not be high enough to stop infections. A way of maintaining antibiotic levels throughout an operation is to give a single dose of antibiotic and then a constant amount of antibiotic by an infusion from the start to the end of the operation. A small single centre test study was previosuly undertaken into antibiotic dosing during bowel operations. One group of patients had a single dose of antibiotic before their operation. The other group had a single dose plus a constant dose of antibiotic until the end of their operation. The project showed patients were happy to take part and that the study was safe. The study helped us identify the correct amounts of antibiotic needed for the patients given the single dose plus a constant dose of antibiotic. This study was conducted at one hospital only, and wasn't big enough to confirm if one treatment was better than another or if results would be similar in other hospitals.

This study will build on the pilot study in a larger feasibility trial, the Colo-Pro_2 trial. It will be run in three hospitals so can assess if the trial design works at different hospitals. We will see if the results suggest one treatment, single dose of antibiotics before an operation, or single dose plus a constant dose of antibiotics throughout an operation, is better. This study will include up to 180 patients having bowel operations as they have a high risk of infection. All patients will be given the same antibiotic which is called cefuroxime. Cefuroxime is already used to stop infections after surgery. Using the same antibiotic in all patients means it is possible to know if differences in the number of infections are due to how the antibiotic is given. The number of infections that happen up to 30 days after operations will be counted. Staff looking after patients after the operation and those counting the infections will not know, unless necessary, the treatment patients received. This means the results won't be influenced by knowledge of the treatment received.

Detailed description: See attached protocol

Eligibility criteria: Inclusion Criteria:

* Undergoing elective colorectal surgery (incision, excision or anastomosis of the large bowel, including anastomosis of small to large bowel)
* Age \>16.
* 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.

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
* Seizure history or epilepsy
* Concurrent use of probenecid
* Current participation in a research project aimed at reducing surgical site infections (SSIs)
* Antibiotics for treatment of a systemic Gram negative infection within 12 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 infection at the time of study entry.
* STARR procedures (stapled trans anal resection of the rectum)
* Weight \<30kg or \>110kg

Primary outcomes:
measure: Recruitment rates
timeFrame: 24 months
measure: Retention rates
timeFrame: 90 days
Secondary outcomes:
measure: Health Care Associated Infection
timeFrame: 30 days
measure: Surgical site infection
timeFrame: 30 days
measure: Microbiological evidence of urinary tract infection (UTI)
timeFrame: 30 days
measure: Antimicrobial consumption after colorectal surgery
timeFrame: 90 days
measure: Antimicrobially resistant infections (AMR infections):
timeFrame: 90 days
measure: C. difficile infection
timeFrame: 90 days
measure: Anastomotic leakage after colorectal surgery
timeFrame: 90 days
measure: Mortality
timeFrame: 90 days
measure: Length of hospital stay
timeFrame: 90 days
measure: Re-admission
timeFrame: 90 days
measure: Cost of healthcare treatment
timeFrame: 90 days
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: TheUniversity of Birmingham
state: West Midlands
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals
state: West Yorkshire
city: Newport
country: United Kingdom
facility: Aneurin Bevan University Health Board
Study officials:
affiliation: The Univeristy of Leeds
name: Andrew Kirby
role: STUDY_CHAIR
References: