Colo-Pro_2: Bolus-continuous Infusion Cefuroxime Prophylaxis for the Prevention of Infections After Colorectal Surgery

NCT05609240 | Recruiting Phase 2

• 1 other identifier: 315251
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

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.

Conditions

Antibiotic Prophylaxis; Colorectal Surgery

Keywords

Cefuroxime; Antibiotic; Colorectal; Prophylaxis; Surgery

Outcome Measures

Primary Outcomes (2)

• Recruitment rates

  Rate of recruitment

  24 months

• Retention rates

  Rate of retention

  90 days

Secondary Outcomes (11)

• Health Care Associated Infection

  30 days

• Surgical site infection

  30 days

• Microbiological evidence of urinary tract infection (UTI)

  30 days

• Antimicrobial consumption after colorectal surgery

  90 days

• Antimicrobially resistant infections (AMR infections):

  90 days

Study Arms (2)

Standard treatment

ACTIVE COMPARATOR

Cefuroxime 1.5 grams intravenous Administered in the hour before surgery and then 4 hourly intra-operatively.

Drug: Cefuroxime

Intervention treatment

ACTIVE COMPARATOR

Cefuroxime loading dose of 2332mg intravenous Administered in the hour before surgery. Following the loading dose a renal function based dosing will be given as a continuous intravenous infusion throughout surgery, as below. Continuous infusion will continue for up to 6 hours when it will return to 4 hourly dosing of cefuroxime at 1.5 grams intravenously, if required. Creatinine clearance (ml/min) and Cefuroxime:Dose per hour (mg/hr) 40-50ml/min=723mg/hr 50-60ml/min=867mg/hr 60-70ml/min=1011mg/hr 70-80ml/min=1155mg/hr \>80ml/min=1227mg/hr

Drug: Cefuroxime

Interventions

Cefuroxime DRUG

See arm/group description

Also known as: Cefuroxime sodium for injection

Intervention treatment; Standard treatment

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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
• 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

Sponsors & Collaborators

• University of Leeds: lead
• University of Birmingham: collaborator
• Aneurin Bevan University Health Board: collaborator

Study Sites (3)

TheUniversity of Birmingham

Birmingham, West Midlands, B15 2TT, United Kingdom

NOT YET RECRUITING

Leeds Teaching Hospitals

Leeds, West Yorkshire, LS17 9EJ, United Kingdom

RECRUITING

Aneurin Bevan University Health Board

Newport, NP20 2UB, United Kingdom

RECRUITING

MeSH Terms

Interventions

Cefuroxime; Injections

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Andrew Kirby

  The Univeristy of Leeds

  STUDY CHAIR

Central Study Contacts

Andrew Kirby

CONTACT

01133923929; a.kirby@leeds.ac.uk

Dermot Burke

CONTACT

0113 3923465; d.burke@leeds.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An anaesthetist will provide the intra-operative intervention and will the subsequently not be involved in the patients follow up or outcome assessment. alternatively, a research nurse not involved in participant follow up will provide the intra-operative intervention.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 8, 2022
• Study Start: May 10, 2023
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)