Clinical trial NCT05964140: The MANTRA Trial (MANdibular TRauma and Antibiotic Use)
Official title: Should we Use Post-operative Antibiotics Following Surgery for Patients With Mandible Fractures? The MANTRA Trial (MANdibular TRauma and Antibiotic Use)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Mandible Fracture
Post-operative Antibiotics
Keywords: Mandible fractures
Antibiotics
Open Reduction and Internal Fixation
Co-amoxiclav
Antibiotic Resistance
Surgical Site Infection
Lead sponsor: East Lancashire Hospitals NHS Trust
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 2841
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Non-inferiority RCT
Primary purpose: TREATMENT

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


Eligibility criteria: 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)

Primary outcomes:
measure: Surgical Site Infection
timeFrame: 30 days
Secondary outcomes:
measure: Return to theatre within 30 days
timeFrame: 30 days
measure: Length of hospital stay
timeFrame: 14 days, 30 days, 180 days
measure: Death and cause of death
timeFrame: 14 days, 30 days, 180 days
measure: Hospital readmission
timeFrame: 30 days
measure: Malunion: fracture non-healing
timeFrame: 180 days
measure: Malocclusion: teeth not meeting as they should
timeFrame: 180 days
measure: Metalwork removal
timeFrame: 14 days, 30 days, 180 days
measure: Overall antibiotic exposure
timeFrame: 14 days, 30 days, 180 days
measure: Antibiotic related adverse events/serious adverse events
timeFrame: 14 days, 30 days, 180 days
measure: Cost
timeFrame: 14 days, 30 days, 180 days
measure: HRQoL (EQ-5D-5L)
timeFrame: 14 days, 30 days, 180 days
Other outcomes:
Locations:
city: Blackburn
country: United Kingdom
facility: East Lancashire Hospitals NHS Trust
state: Lancashire
city: Blackburn
country: United Kingdom
facility: East Lancashire Hospitals NHS Trust
state: Lancashire
Study officials:
affiliation: Consultant OMFS H&N Surgeon ELHT
name: Panayiotis Kyzas, PhD
role: PRINCIPAL_INVESTIGATOR
References: