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The MANTRA Trial (MANdibular TRauma and Antibiotic Use)

Phase 3
Recruiting
Conditions
Post-operative Antibiotics
Mandible Fracture
Interventions
Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures
Registration Number
NCT05964140
Lead Sponsor
East Lancashire Hospitals NHS Trust
Brief Summary

1. FULL TITLE OF THE PROJECT Should we use post-operative antibiotics following surgery for patients with mandible fractures? The MANTRA trial (MANdibular TRauma and Antibiotic use)

2. SUMMARY OF RESEARCH (ABSTRACT) Research Question: Are post-operative antibiotics required following surgery for patients with mandible fractures? Background: Mandible fractures are the commonest facial fractures needing surgery and account for a significant percentage of the acute workload in Oral \& Maxillofacial Surgery (OMFS) units. The UK records over 6000 new cases per year. Patients having surgery for mandible fractures have a theoretical risk of developing surgical site infection, due to the proximity of the fracture lines to the oral cavity microbes and the presence of foreign body (titanium fixation miniplates). For this reason, clinicians often prescribe antibiotics after surgery, to reduce the risk of infection. Previous systematic reviews and a multicentre cohort study performed by this team, revealed significant clinical variation in post-operative antibiotic prescription amongst UK OMFS clinicians and the presence of clinical equipoise. Antibiotic overuse can lead to antibiotic resistance and other antibiotic-related side effects; judicious antibiotic use and stewardship is of paramount importance.

Aim: To determine whether post-operative antibiotics are required at all, following surgery for mandible fractures, and, if so, what is the most clinically- and cost-effective regimen

Objectives:

Primary Objective To conduct a Randomized Controlled Trial (MANTRA) in order to establish the non-inferiority (or not) of not giving post-operative antibiotics versus 2 other post-operative antibiotic regimens. An internal pilot phase will optimise recruitment and retention.

Secondary Objectives

* Measure the cost-effectiveness of the proposed antibiotic pathways

* Assess patient and clinician acceptability to change clinical practice

* Process evaluation to inform dissemination and implementation Methods: The investigators designed and propose the MANTRA RCT to compare 3 post-operative antibiotic approaches to prevent Surgical Site Infections (SSIs) following surgery for mandible fractures. The MANTRA trial is a large open label, multicentre study in NHS OMFS units. The 3 study arms represent the most common clinical pathways in the UK based on previous work; the control group is the approach prescribed by most UK OMFS clinicians. All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g, if no penicillin allergy, which is the most commonly used prophylactic antibiotic currently) on induction of anaesthesia, prior to their surgery.

The participants will be randomised to the following (1:1:1):

Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav 1.2g Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control).

Trial processes will be optimised by an internal pilot phase ensuring we recruit, randomise, and retain participants with clear progression criteria. We will also conduct cost-effectiveness analyses and process evaluation for dissemination and implementation

Timeline:

Start of grant: 1st July 2023 Start of RCT / pilot: 1st January 2024 End of pilot: 30th June 2024 End of recruitment: 31st December 2026 End of follow-up: 30th June 2027 Completion: 31st December 2027

Impact and dissemination:

* Practice changing outputs that standardise the use of antibiotics in mandible fractures in the NHS and provide a framework for other surgical prophylaxis research

* A bespoke clinical dissemination plan via an engagement and training legacy

* Cost-effectiveness data to inform policy making

* A research legacy and change of culture in the specialty of OMFS

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2841
Inclusion Criteria
  • Ability to provide written informed consent
  • Age≥18 years
  • Hospital episode of mandible fracture(s)
  • Planned treatment is surgery - (ORIF with titanium miniplates)
Exclusion Criteria
  • Isolated mandibular condylar fractures
  • Existing fracture site infection
  • Immunocompromised (transplant patients, haematological malignancies, HIV/AIDS) - a clear definition will be provided in the protocol
  • Pathological fracture (e.g., malignancy, osteoradionecrosis, cysts, Medication-Related Osteonecrosis of the Jaws [MRONJ])
  • Fractures open to skin
  • Inability to provide written informed consent
  • Other injuries or infections mandating ongoing post-operative antibiotics (e.g., panfacial fractures with mandible fracture component)
  • Patients allergic to first and second-line antibiotic prophylaxis (as outlined above)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Group ADifferent post-operative antibiotic regimens following surgical treatment of mandible fracturesGroup A: One induction IV dose
Group BDifferent post-operative antibiotic regimens following surgical treatment of mandible fracturesGroup B: One induction IV dose and 2 further postoperative IV doses
Group CDifferent post-operative antibiotic regimens following surgical treatment of mandible fracturesGroup C: One IV dose of antibiotics on induction and 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy
Primary Outcome Measures
NameTimeMethod
Surgical Site Infection30 days

Incidence of Surgical Site Infection (CDC definition) following surgery for mandible fractures

Secondary Outcome Measures
NameTimeMethod
Return to theatre within 30 days30 days
Malocclusion: teeth not meeting as they should180 days

When the fracture reduction failed to restore the dental occlusion

Metalwork removal14 days, 30 days, 180 days

When the fixation titanium miniplates need to be removed at any point and for any reason

Antibiotic related adverse events/serious adverse events14 days, 30 days, 180 days
Hospital readmission30 days
Malunion: fracture non-healing180 days

Fibrous union, fracture mobility, absence of callus formation

HRQoL (EQ-5D-5L)14 days, 30 days, 180 days

Health Related Quality of Life

Length of hospital stay14 days, 30 days, 180 days
Death and cause of death14 days, 30 days, 180 days
Overall antibiotic exposure14 days, 30 days, 180 days
Cost14 days, 30 days, 180 days

Trial Locations

Locations (1)

East Lancashire Hospitals NHS Trust

🇬🇧

Blackburn, Lancashire, United Kingdom

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