Hyperbaric Oxygen for the Prevention of OsteoradioNecrosis

ISRCTN	ISRCTN39634732
DOI	https://doi.org/10.1186/ISRCTN39634732
Protocol serial number	2
Sponsor	University of Liverpool (UK)
Funder	Cancer Research UK (ref: C23033/A9397)

Submission date: 21/05/2008
Registration date: 13/06/2008
Last edited: 18/11/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-study-looking-at-a-treatment-to-prevent-jaw-bone-damage-in-head-and-neck-cancer

Contact information

Mr Richard Shaw
Scientific

Regional Maxillofacial Unit
University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom

Phone	+44 (0)151 529 5290
Email	richardshaw@liv.ac.uk

Study information

Primary study design	Interventional
Study design	Multicentre randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible
Study acronym	HOPON
Study objectives	The aim of this study is to determine the benefit of hyperbaric oxygen (HBO) in the prevention of osteoradionecrosis (ORN) subsequent to a surgical procedure in the "at risk" irradiated mandible. This study is designed as a randomised control multi-centre feasibility study.
Ethics approval(s)	Central Manchester Research Ethics Committee on 28/04/2008 (ref: 08/H1008/32)
Health condition(s) or problem(s) studied	Osteoradionecrosis subsequent to a surgical procedure in an irradiated mandible
Intervention	Arm 1: Standard management: 1. Pre- and post-operative chlorohexidine1 mouthwash 0.2% - use 10 ml (i.e. one capful) washed around the mouth for around 1 minute and spat out, three times daily for 5 days post-operatively. 1.1. In case of chlorohexidine allergy use warm salt mouthwash at 1 teaspoon per cup of warm water. 2. Oral antibiotics: amoxicillin 3 g oral 1 hour pre-operatively (or 1 g intravenously), and 250 mg three times a day (tds) x 5 days post-operatively 2.1. In penicillin allergy: Orally either 600 mg tablet, or same dose of 75 mg/5 ml suspension if tablets not tolerated, 1 hour pre-operatively or intravenously 600 mg at time of surgery, and 200 mg metronidazole (patients should be warned of interaction between alcohol and metronidazole) tds x 5 days post-operatively Arm 2: Standard management plus HBO Patients will undergo 20 HBO treatments prior to surgery followed by a further 10 HBO treatments. HBO will comply with dive table RN66. For each HBO treatment, patients are compressed to 2.4 ata while sitting in an appropriate British Hyperbaric Association recognised hyperbaric chamber. Patients breathe 100% oxygen at pressure via a transparent hood. The total time at 2.4 ata is 90 minutes. During the final 10 minutes of oxygen breathing, the chamber is depressurised to ambient atmospheric pressure at a linear rate (14.3 kpa/min). 3. All participants will be operated with a minimally traumatic surgical technique after the standard management with or without HBO.
Intervention type	Other
Primary outcome measure(s)	Mucosal healing and/or the presence of necrotic bone at 6 months following surgery, measured by the following: 1. Clinical assessment in centre 2. Clinical photograph with in-photograph ruler 3. Radiographic using orthopantomogram (OPT) The primary outcome will be based on a blinded assessment of anonymised clinical photograph and radiograph by a central committee consisting of experienced clinicians in the field.
Key secondary outcome measure(s)	1. Mucosal healing at 3 months following surgery (measured as at 6 months following surgery) 2. Severity of cases of diagnosed osteoradionecrosis, with clinical and radiographic recordings of severity made according to the following: 2.1. Grade I: ORN confined to alveolar bone 2.2. Grade II: ORN limited to the alveolar bone and/or mandible above the level of inferior alveolar canal 2.3. Grade III: ORN involving the mandible below the level of inferior alveolar canal and ORN with a skin fistula and/or pathologic fracture 3. Pain: patient questionnaire at 3 and 6 months 4. Quality of life (QoL): prior to randomisation but following consent, and at 3 and 6 months (as determined by a modified University of Washington) 5. Head and Neck QoL questionnaire (modified) at baseline, 3 and 6 months 6. Adverse events in HBO arm related to hyperbaric oxygen treatment, monitored throughout trial 7. Admissions, operations, complications (e.g. major bleeding, sepsis), monitored throughout trial 8. Mortality. Patients will be followed up until death or 6 months. 9. Implant retention (where appropriate) and outcomes of ORN (where appropriate) at 12 and 24 months following surgery
Completion date	31/05/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	200
Key inclusion criteria	1. Both males and females, age >18 years 2. Prior history of external beam radiotherapy (dose >50 Gy) to mandible or prior history of brachytherapy with equivalent radiation dose as above 3. No evidence of cancer recurrence 4. Condition requiring surgery to mandible (commonest examples but not limited to: dental extraction, implant placement, surgical tooth, cyst or osteosynthesis plate removal) 5. Patient has read and understood information leaflet and is willing to be randomised 6. Patient competent to consent and psychologically/ physically fit for HBO
Key exclusion criteria	1. Known contraindications to HBO: 1.1. Lung disease: Severe chronic obstructive airways disease; bullous lung disease, acute or chronic pulmonary infection; uncontrolled asthma, untreated pneumothorax 12. Middle ear disease (such as previous middle ear operations, eustachian tube dysfunction or recurrent attacks of vertigo) that proves refractory to simple interventions such as grommet insertion 2. Prior hyperbaric oxygen therapy 3. Prior diagnosis of osteoradionecrosis of the mandible 4. Previous surgery for osteoradionecrosis 5. Any history of systemic bisphosphonate therapy, pentoxyphylline or tocopherol 6. Pregnancy
Date of first enrolment	01/06/2008
Date of final enrolment	31/05/2014

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Regional Maxillofacial Unit

Liverpool
L9 7AL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

18/11/2016: No publications found in PubMed, verifying study status with principal investigator.
22/02/2011: The anticipated end date for this trial was updated from 31/05/2010 to 31/05/2014 and the target participant number was increased from 50 to 200.