The MANTRA Trial (MANdibular TRauma and Antibiotic Use)

Mandible Fracture Clinical Trial

— MANTRA  

Official title:

Should we Use Post-operative Antibiotics to Prevent Surgical Site Infections (SSIs) Following Surgery for Patients With Mandible Fractures? The MANTRA Trial - a Phase III, Non-inferiority, Non-blinded, Pragmatic Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05964140
• Other study ID #: DEV008
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: East Lancashire Hospitals NHS Trust
• Contact: Panayiotis Kyzas
• Phone: +447505402640
• Email: Panayiotis.Kyzas[@]elht.nhs.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2907
• Est. completion date: December 31, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Fractures, Bone
• Mandible Fracture
• Mandibular Fractures

Intervention

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).

Locations

Country	Name	City	State
United Kingdom	East Lancashire Hospitals NHS Trust	Oldham	Greater Manchester

Sponsors (1)

Lead Sponsor	Collaborator
East Lancashire Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

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