HOPON

Title

HOPON: Hyperbaric Oxygen for the Prevention of Osteoradionecrosis.

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
III	Treatment	Open	Over 18	University of Liverpool and Aintree University Hospital NHS Foundation trust	EUDRACT No: 2007-006225-27 ISRCTN No: 39634732

Trial Description

Purpose

One complication of radiotherapy for head and neck cancer is osteoradionecrosis (ORN) of the jaws. Osteoradionecrosis (ORN) describes the process where irradiated bone undergoes necrosis and becomes exposed through the investing soft tissues for a period of at least 3 months. The most important risk factor for ORN is surgical trauma, commonly dental extractions in an irradiated jaw, but ORN can also occur spontaneously. ORN is painful and debilitating, sometimes requiring surgical resection of the jaw and/or hyperbaric oxygen (HBO) treatments. The morbidity and mortality of osteoradionecrosis is significant and treatment outcomes often unsatisfactory.

Eligibility

Age > 18 years
Prior history of external beam radiotherapy (dose > 50Gy) to mandible or prior history of brachytherapy with equivalent radiation dose as above.
No evidence of cancer recurrence
Condition requiring surgery to mandible (commonest examples but not limited to: dental extraction, implant placement, surgical tooth removal, cyst enucleation)
Patient has read and understood information leaflet and is willing to be randomised.
Patient competent to consent and psychologically / physically fit for HBO.
No known contraindications to HBO

Lung disease: Severe chronic obstructive airways disease; bullous lung disease, acute or chronic pulmonary infection; uncontrolled asthma, untreated pneumothorax
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

No prior hyperbaric oxygen therapy
No prior diagnosis of osteoradionecrosis of the mandible
No previous surgery for osteoradionecrosis
No history of systemic bisphosphonate therapy, pentoxyphylline or tocopherol.
Not Pregnancy

Treatment/Intervention

This multicentre randomised feasibility study will test only feasibility measures in the first instance. These include adequate recruitment, acceptability of randomisation, retention, completeness of data, protocol violations and loss to follow-up. If this study proves feasible an application will be made to upgrade to a phase III trial. Provided the phase III trial is approved, this will have the following null hypothesis: Hyperbaric oxygen has no value in the prevention of osteoradionecrosis of the mandible following surgery

Trial Endpoints

To determine the benefit of HBO in the prevention of osteoradionecrosis (ORN) subsequent to a surgical procedure in the "at risk" irradiated mandible

Primary Outcome

Mucosal healing at 6 months following surgery

Secondary outcomes

Mucosal healing at 3 months following surgery (measured by clinical photograph with in-photograph ruler).
Severity of cases of diagnosed osteoradionecrosis, with clinical and radiographic recordings of severity made according to: Notani K. et al., Head & Neck 2003: 25:181-186
Pain: patient questionnaire at 3 and 6 months
Radiographic appearance: orthopantomogram (OPT) at 3 and 6 months
Clinical photographs at 3 and 6 months
Quality of life (QoL): at 3 and 6 months (as determined by the University of Washington
Head and Neck QoL questionnaire)
Adverse events in HBO arm related to hyperbaric oxygen treatment
Admissions, operations, complications (e.g. major bleeding, sepsis)
Mortality
Implant retention (where appropriate) and outcomes of ORN (where appropriate) at 12 and 24 months following surgery

Trial Lead Organisations

University Hospital Aintree NHS Foundation Trust
University of Liverpool
Chief Investigator: Mr Richard Shaw

Trial Sites

There are now 19 sites open in the trial:

Aberdeen Royal Infirmary, Aberdeen (Dr. John Ross)
Derriford Hospital, Plymouth (Dr. David Courtney)
Glan Clwyd Hospital, Rhyl (Mr. Chris Lloyd)
Gloucestershire Royal Hospital, Gloucester (Mr. Charles Perkins)
Guys & St Thomas Hospital, London (Prof. Mark McGurk)
Leeds General Infirmary, Clarendon Way (Dr. Sheila Fisher)
Liverpool University Dental Hospital, Liverpool (Dr. Christopher Butterworth)
Manchester Royal Infirmary, Manchester (Mr. Brian Musgrove)
Musgrove Park Hospital, Taunton (Dr. Manuel Blanco-Guzman)
North Manchester General Hospital, Manchester ( Robert Woodwards)
North of England Hyperbaric Service, Hull (Dr. Gerard Purdy)
North West Emergency Recompression Unit, Murrayfield Hospital, (Dr. John Harrison)
St Bartholomews Hospital, London (Prof. Iain Hutchison)
St Lukes Hospital, Bradford (Mr. James McCaul)
The Hyperbaric Medical Centre, Plymouth (Dr. Phil Bryson)
University Hospital Aintree, Liverpool (Mr. Richard Shaw)
University Hospital Birmingham, Birmingham (Dr. Keith Webster)
Whipps Cross University Hospital, London (Dr. Mihaela Ignatescu)
Yeovil District Hospital, (Dr. Manuel Blanco-Guzman)

The following sites have expressed an interest:

Copenhagen University Hospital, DK-2100 Copenhagen Ø (Mr. Lone Forner)
Hyperbaric Medicine Unit, Royal Hospital Haslar, Portsmouth (Dr. Mark Alec-Glover)
Queen Alexandra Hospital, Portsmouth (Prof. Peter Brennan)
Royal Derby Hospital, Derby (Mr David Laugharne)
Royal Marsden Hospital SW3 6JJ, London (Dr Cyrus Kerawala)
St Richards Hospital, Chichester (Dr Mark Glover)
The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, (Dr. Ludi Smeele)
University College Hospital, London (Dr Colin Liew)

Registry Information

Official Title