Condition category
Injury, Occupational Diseases, Poisoning
Date applied
21/05/2008
Date assigned
13/06/2008
Last edited
18/11/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

http://www.liv.ac.uk

Funders

Funder type

Charity

Funder name

Cancer Research UK (ref: C23033/A9397)

Alternative name(s)

CRUK

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

Publication citations

Additional files

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.