The MANTRA Trial (MANdibular TRauma and Antibiotic Use) (MANTRA)

Should we Use Post-operative Antibiotics Following Surgery for Patients With Mandible Fractures? The MANTRA Trial (MANdibular TRauma and Antibiotic Use)

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

Study Overview

• Status: Recruiting
• Conditions: Mandible Fracture; Post-operative Antibiotics
• Intervention / Treatment: Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures

• Study Type: Interventional
• Enrollment (Estimated): 2841
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Panayiotis Kyzas; Phone Number: +447505402640; Email: Panayiotis.Kyzas@elht.nhs.uk

Study Locations

• United Kingdom
  • Lancashire
    • Blackburn, Lancashire, United Kingdom, BB2 3HH
      • Recruiting
      • East Lancashire Hospitals NHS Trust
      • Contact: Panayiotis Kyzas; Phone Number: 07505402640; Email: Panayiotis.Kyzas@elht.nhs.uk
    • Blackburn, Lancashire, United Kingdom, BB2 3HH
      • Not yet recruiting
      • East Lancashire Hospitals NHS Trust
      • Contact: Panayiotis Kyzas; Phone Number: 07505402640; Email: Panayiotis.Kyzas@elht.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

All adult patients aged 18 years or over with mandible fractures requiring surgery. Most of these patients will be identified from the A&E department via the on-call OMFS team or seen in dedicated OMFS trauma clinics. A small proportion of our study population will be seen in an OMFS clinic following referral from GP/GDP.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Group A: One induction IV dose	Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures; The 3 study arms represent the most common antibiotic regimens used in current clinical practice following surgery for mandible fractures. The control group is the most common approach. All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g), if no penicillin allergy, 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).
Experimental: Group B; Group B: One induction IV dose and 2 further postoperative IV doses	Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures; The 3 study arms represent the most common antibiotic regimens used in current clinical practice following surgery for mandible fractures. The control group is the most common approach. All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g), if no penicillin allergy, 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).
Active Comparator: Group C; Group 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	Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures; The 3 study arms represent the most common antibiotic regimens used in current clinical practice following surgery for mandible fractures. The control group is the most common approach. All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g), if no penicillin allergy, 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Site Infection	Incidence of Surgical Site Infection (CDC definition) following surgery for mandible fractures	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital readmission		30 days
Return to theatre within 30 days		30 days
Length of hospital stay		14 days, 30 days, 180 days
Death and cause of death		14 days, 30 days, 180 days
Malunion: fracture non-healing	Fibrous union, fracture mobility, absence of callus formation	180 days
Malocclusion: teeth not meeting as they should	When the fracture reduction failed to restore the dental occlusion	180 days
Metalwork removal	When the fixation titanium miniplates need to be removed at any point and for any reason	14 days, 30 days, 180 days
Overall antibiotic exposure		14 days, 30 days, 180 days
Antibiotic related adverse events/serious adverse events		14 days, 30 days, 180 days
Cost		14 days, 30 days, 180 days
HRQoL (EQ-5D-5L)	Health Related Quality of Life	14 days, 30 days, 180 days

Collaborators and Investigators

• Sponsor: East Lancashire Hospitals NHS Trust
• Investigators: Principal Investigator: Panayiotis Kyzas, PhD, Consultant OMFS H&N Surgeon ELHT

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Antibiotics; Surgical Site Infection; Open Reduction and Internal Fixation; Antibiotic Resistance; Co-amoxiclav; Mandible fractures
• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Postoperative Complications; Pathologic Processes; Infections; Fractures, Bone; Craniocerebral Trauma; Trauma, Nervous System; Wound Infection; Facial Injuries; Jaw Fractures; Maxillofacial Injuries; Skull Fractures; Pathological Conditions, Signs and Symptoms; Surgical Wound Infection; Mandibular Fractures; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: DEV008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No