Using ultrasound to improve antibiotic treatment in infected burns: a feasibility study

ISRCTN	ISRCTN42000162
DOI	https://doi.org/10.1186/ISRCTN42000162
Integrated Research Application System (IRAS)	1013208
Sponsor	Buckinghamshire Healthcare NHS Trust
Funder	NIHR Oxford Biomedical Research Centre

Submission date: 25/11/2025
Registration date: 17/02/2026
Last edited: 17/02/2026

Recruitment status: Not yet recruiting
Overall study status: Ongoing
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
This study will assess whether ultrasound-activated microbubbles with antibiotics are safe, and whether a larger scale study is feasible. Some indications of the impact of the use of ultrasound-activated microbubbles with antibiotics on patient recovery will also be made.

Who can participate?
The study will include adults aged 18 or older who are admitted to the regional burn unit at Buckinghamshire Healthcare NHS Trust. They must have a clinically infected superficial or partial-thickness thermal burn affecting no more than 4% of their total body surface area.

What does the study involve?
People with small, infected burns will be randomly assigned to receive either microbubbles with antibiotics or a placebo (a treatment that looks the same but has no active medication). The treatment will be given alongside normal wound care and antibiotics. Researchers will check for any side effects, see how easy it is to use the treatment, and measure how well the infection heals. If this study is successful, it could lead to larger trials and, in the future, a new way to treat infections more effectively.

What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
Participation in this study is not expected to involve significant risks beyond normal hospital treatment for an infected burn. However, some temporary discomfort or inconvenience may occur. The following outlines possible risks and the steps taken to minimise them.
1. Physical discomfort or local skin irritation
The study involves applying a gel containing microbubbles and, in some cases, gentamicin to the burn wound, followed by a brief ultrasound treatment (30 seconds–2 minutes). Some participants may experience mild warmth, stinging, or tenderness.
Minimisation: Treatments will be performed by trained staff under sterile conditions, using clinically approved equipment and low ultrasound settings. Participants will be monitored during and after treatment, and any discomfort or reaction will be promptly managed using standard care.
2. Allergic reactions
A small number of people may be allergic to one of the products used (gentamicin, microbubble contrast, or the gel base).
Minimisation: All participants will be screened for known allergies or sensitivities before enrolment. Anyone with a history of allergy to these products will be excluded. Emergency equipment and trained staff will be available if a reaction occurs. The likelihood of allergy is very low as these products are routinely used in the NHS.
3. Theoretical risk of bacterial spread or systemic infection
There is a theoretical risk that ultrasound could temporarily increase tissue permeability and allow bacteria to move deeper into the skin.
Minimisation: This risk is considered extremely low. Participants will continue to receive standard antibiotics and wound dressings. They will be monitored for any signs of worsening infection or fever, and any concerns will be managed immediately according to standard clinical practice.
4. Blood tests and wound swabs
Participants will have wound swabs taken before and after treatment sessions, and routine blood tests performed as part of normal care. These may cause mild discomfort.
Minimisation: Swabs and blood samples will be collected by experienced staff using standard techniques, timed to coincide with routine procedures to avoid additional burden.
5. Time and inconvenience
All study procedures will occur during the participant’s hospital stay, so no extra visits or travel are required. Each treatment session will last around 30–45 minutes, including set-up, treatment, and brief questionnaires.
Minimisation: Procedures will align with routine dressing changes and ward rounds. Questionnaires are brief (under five minutes) and can be completed at the bedside.
6. Confidentiality and data security
Photographs and imaging of the wound will be taken to monitor healing. Although these will be anonymised, there is a minimal risk of loss of confidentiality.
Minimisation: All data and images will be coded using a study ID and stored on secure NHS servers with restricted access. Identifiable features will be excluded wherever possible, and no data will be stored on personal or portable devices.
7. Psychological or emotional distress
Discussing or viewing wound photographs may cause mild distress or embarrassment for some participants.
Minimisation: Participants will be treated sensitively and can choose not to view their images or withdraw from the study at any time without affecting their care.
The overall level of risk is low. All clinical components (ultrasound, gentamicin, and wound care products) are routinely used in NHS practice. Additional study activities (imaging and questionnaires) are minimal, non-invasive, and designed to reduce participant burden. Participants will receive full information about all potential risks before giving consent and may withdraw at any time without affecting their clinical treatment or care.

Where is the study run from?
Buckinghamshire Healthcare NHS Trust (UK)

When is the study starting and how long is it expected to run for?
March 2026 to January 2028

Who is funding the study?
NIHR Oxford Biomedical Research Centre (UK)

Who is the main contact?
Prof Fadi Issa fadi.issa@nhs.net

Contact information

Prof Fadi Issa
Principal investigator, Public, Scientific

Stoke Mandeville Hospital
Aylesbury
HP21 8AL
United Kingdom

ORCID ID	0000-0002-8279-7732
Phone	+44 (0)1296 418140
Email	fadi.issa@nhs.net

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Blinded (masking used)
Control	Active
Assignment	Parallel
Purpose	Treatment
Scientific title	Feasibility of ultrasound-activated microbubble–assisted topical antibiotic delivery in infected partial-thickness burns: a randomised controlled trial.
Study objectives	To assess the safety and feasibility of using ultrasound-activated microbubbles to enhance topical antibiotic delivery in the management of infected partial-thickness burn wounds. The study will determine whether the procedure is safe, well tolerated, and practical to deliver in an inpatient burn care setting, and whether progression to a larger definitive trial is feasible. To explore the effect of ultrasound-activated microbubbles on wound infection resolution, bacterial load, and healing outcomes. Secondary objectives also include assessing patient tolerability, acceptability, and willingness to use the intervention in future clinical practice, alongside evaluating changes in microbiological findings, wound appearance, and patient-reported outcomes (pain and satisfaction).
Ethics approval(s)	Approved 26/01/2026, London - Dulwich Research Ethics Committee (Health Research Authority, 2nd Floor, 2 Redman Place, Stratford, London, E20 1JO, United Kingdom; +442071048276; dulwich.rec@hra.nhs.uk), ref: 25/LO/0907
Health condition(s) or problem(s) studied	Medical condition: Infected partial-thickness burn wounds (superficial to deep partial-thickness confluent wounds affecting <4% TBSA). Medical condition in lay language: Infections in small burn wounds — specifically partial-thickness burns that have become infected and require treatment during hospital admission. Therapeutic areas: Diseases [C] - Bacterial Infections and Mycoses [C01]
Intervention	This is a single-centre, randomised controlled feasibility study with four parallel arms (1:1:1:1). Participants are inpatient adult burn patients with clinically infected partial-thickness burns managed without skin grafting. All groups receive standard of care, comprising systemic antibiotics as per local burns SOPs, wound cleaning, antiseptic dressing (Bactigras), and routine inpatient monitoring. All arms are followed during admission and routine outpatient care until wound healing. • Arm 1 Standard of Care (Primary Control, open label): Participants receive standard wound care and systemic antibiotics only. No study gel or ultrasound is applied. • Arm 2 Standard of Care + Ultrasound-activated microbubbles with gentamicin (Intervention) Participants receive topical gel containing ultrasound-responsive microbubbles (Luminity®) combined with gentamicin 80 mg (40 mg/mL formulation). Dose: 80 mg gentamicin per application (topical) Route: Topical application to wound surface Frequency: Once daily Duration: Up to 3 treatment sessions Ultrasound parameters: 1 MHz ultrasound applied for 30 seconds to 2 minutes per treatment site • Arm 3 Standard of Care + Ultrasound-activated microbubbles without gentamicin (Treatment Control 1) Participants receive topical gel containing ultrasound-responsive microbubbles (Luminity®) but without antibiotic. Route: Topical application to wound surface Frequency: Once daily Duration: Up to 3 treatment sessions Ultrasound parameters: 1 MHz ultrasound applied for 30 seconds to 2 minutes per treatment site • Arm 4 Standard of Care + Microbubbles with gentamicin without ultrasound activation (Treatment Control 2) Participants receive topical gel containing ultrasound-responsive microbubbles (Luminity®) combined with gentamicin 80 mg (40 mg/mL formulation) but without ultrasound activation. Dose: 80 mg gentamicin per application (topical) Route: Topical application to wound surface Treatment is delivered once daily for a maximum of three sessions alongside standard care. Participants exit the study at discharge, clinical resolution, completion of treatment, or withdrawal. Randomisation is performed using a computer-generated sequence with permuted blocks. Allocation is concealed using sequentially numbered sealed envelopes generated via an online randomisation tool. Treatment preparation and the ultrasound unit operation are performed by an unblinded investigator who is not involved in patient care. Investigators, participants, and outcome assessors are blinded across the three treatment arms.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Luminity® [Perflutren (approved INN)] , Gentamicin 10 mg/mL Solution for Injection or Infusion [Gentamicin (INN — approved)]
Primary outcome measure(s)	Safety measured using the incidence of adverse events recorded on electronic Case Report Forms at consent until the end of study participation (hospital discharge or completion of follow-up) Feasibility measured using participant recruitment rate, treatment adherence, and retention rate recorded in study databases at the start of the recruitment period until completion of participant follow-up
Key secondary outcome measure(s)	Wound infection resolution measured using the change in bacterial presence on wound swabs using standard microbiological culture, semi-quantitative growth categorisation (heavy growth, moderate growth, scanty growth), species identification and antimicrobial susceptibility testing at baseline and prior to each treatment session Wound healing rate measured using standard clinical wound assessment (size, depth, infection signs), standardised wound photography, and Laser Doppler Imaging (LDI) perfusion assessment, at baseline and prior to each treatment session until wound healing or discharge Tolerability: Comfort measured using a 0–10 Visual Analogue Scale at after each treatment session Tolerability: Acceptability measured using a Likert scale questionnaire at the end of treatment or discharge Tolerability: Willingness to use treatment in future clinical practice measured using a post-study questionnaire at the end of participation (treatment completion or discharge)
Completion date	01/01/2028

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	100 Years
Sex	All
Target sample size at registration	80
Key inclusion criteria	1. Adults aged ≥18 years. 2. Admitted to the regional burn unit at Buckinghamshire Healthcare NHS Trust. 3. Clinically infected superficial or partial-thickness thermal burn wounds (superficial to deep partial-thickness) affecting ≤4% total body surface area (TBSA). 4. “Clinically infected” is defined by clinical signs observed by the treating team (e.g. erythema, pain, swelling, purulence) and symptoms reported by the patient. 5. Able to provide informed consent and with mental capacity to understand the study requirements. 6. Inpatients with burns being managed without surgical grafting. 7. Patients who have undergone surgical debridement (e.g. Versajet) but not grafting are eligible. 8. Willing and able to comply with study procedures and follow-up during hospital admission.
Key exclusion criteria	The participant may not enter the study if ANY of the following apply: Trial design–related: 1. Wounds involving >4% total body surface area (TBSA) 2. Full-thickness or chemical burns 3. Wounds requiring grafting as part of treatment 4. Participation in another clinical trial involving burn treatment or antibiotics Products: 1. Optilube: Known allergy or hypersensitivity to any component of Optilube 2. Luminity: Known allergy or hypersensitivity to any excipients in Luminity 3. Gentamicin: Known allergy or hypersensitivity to gentamicin or any of its excipients 4. Known contraindication to gentamicin use 5. Concomitant use of nephrotoxic or ototoxic medications 6. History of serious aminoglycoside toxicity 7. Pre-existing auditory or vestibular disease Ultrasound-related: 1. Presence of metallic implants within or near the treatment area (risk of heating) 2. Presence of other dermatoses in the treatment area (e.g. eczema, psoriasis) 3. Known or suspected pregnancy, or currently breastfeeding 4. Presence of methicillin-resistant Staphylococcus aureus (MRSA) infection 5. Myasthenia gravis 6. Current treatment with immune-modulating drugs (e.g. corticosteroids, anti-rejection therapy, chemotherapy)
Date of first enrolment	31/03/2026
Date of final enrolment	01/10/2027

Locations

Countries of recruitment

United Kingdom

Study participating centre

Stoke Mandeville Hospital

Mandeville Road
Aylesbury
HP21 8AL
England

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan

Editorial Notes

11/02/2026: ISRCTN received notification of combined HRA/MHRA approval for this trial on 11/02/2026.
25/11/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)