Contact information
Type
Scientific
Primary contact
Mr Richard Shaw
ORCID ID
Contact details
Regional Maxillofacial Unit
University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom
+44 (0)151 529 5290
richardshaw@liv.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2
Study information
Scientific title
A randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible
Acronym
HOPON
Study hypothesis
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
Central Manchester Research Ethics Committee on 28/04/2008 (ref: 08/H1008/32)
Study design
Multicentre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Prevention
Patient information sheet
Patient information can be found at: http://www.lctu.org.uk/docs/trialdocs.html
Condition
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
Phase
Phase III
Drug names
Primary outcome measures
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.
Secondary outcome measures
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
Overall trial start date
01/06/2008
Overall trial end date
31/05/2014
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Added 22/02/2011: 200 (50 at time of registration)
Participant 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
Recruitment start date
01/06/2008
Recruitment end date
31/05/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Regional Maxillofacial Unit
Liverpool
L9 7AL
United Kingdom
Sponsor information
Organisation
University of Liverpool (UK)
Sponsor details
Foundation Building
Brownlow Hill
Liverpool
L69 7ZX
United Kingdom
+44 (0)151 794 2000
Ethics@liverpool.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (ref: C23033/A9397)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary