The MANTRA Trial (MANdibular TRauma and Antibiotic Use)

NCT05964140 | Recruiting Phase 3 DMC

• 1 other identifier: DEV008
• Study Type: interventional
• Target: 2,841
• Locations: 1 country
• Sites: 2

Brief Summary

• 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

Conditions

Post-operative Antibiotics; Mandible Fracture

Keywords

Mandible fractures; Antibiotics; Open Reduction and Internal Fixation; Co-amoxiclav; Antibiotic Resistance; Surgical Site Infection

Outcome Measures

Primary Outcomes (1)

• Surgical Site Infection

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

  30 days

Secondary Outcomes (11)

• 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

• Hospital readmission

  30 days

• Malunion: fracture non-healing

  180 days

Study Arms (3)

Group A

EXPERIMENTAL

Group A: One induction IV dose

Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures

Group B

EXPERIMENTAL

Group B: One induction IV dose and 2 further postoperative IV doses

Drug: Different post-operative antibiotic regimens following surgical treatment of mandible fractures

Group C

ACTIVE COMPARATOR

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

Interventions

Different post-operative antibiotic regimens following surgical treatment of mandible fractures DRUG

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).

Group A; Group B; Group C

Eligibility Criteria

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

You may qualify if:

• Ability to provide written informed consent
• Age≥18 years
• Hospital episode of mandible fracture(s)
• Planned treatment is surgery - (ORIF with titanium miniplates)

You may not qualify if:

• 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)

Sponsors & Collaborators

• East Lancashire Hospitals NHS Trust: lead

Study Sites (2)

East Lancashire Hospitals NHS Trust

Blackburn, Lancashire, BB2 3HH, United Kingdom

RECRUITING

East Lancashire Hospitals NHS Trust

Blackburn, Lancashire, BB2 3HH, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Mandibular Fractures; Surgical Wound Infection

Condition Hierarchy (Ancestors)

Jaw Fractures; Maxillofacial Injuries; Facial Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Skull Fractures; Fractures, Bone; Wounds and Injuries; Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Panayiotis Kyzas, PhD

  Consultant OMFS H&N Surgeon ELHT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Panayiotis Kyzas

CONTACT

+447505402640; Panayiotis.Kyzas@elht.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Non-inferiority RCT

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: July 27, 2023
• Study Start: December 6, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

GB (2)