Abstract
BackgroundOsteoradionecrosis of the mandible is the most common serious complication of radiotherapy for head and neck malignancy. For decades, hyperbaric oxygen has been employed in efforts to prevent those cases of osteoradionecrosis that are precipitated by dental extractions or implant placement. The evidence for using hyperbaric oxygen remains poor and current clinical practice varies greatly. We describe a protocol for a clinical trial to assess the benefit of hyperbaric oxygen in the prevention of osteoradionecrosis during surgery on the irradiated mandible.Methods/designThe HOPON trial is a phase III, randomised controlled, multi-centre trial. It employs an unblinded trial design, but the assessment of the primary endpoint, i.e. the diagnosis of osteoradionecrosis, is assessed on anonymised clinical photographs and radiographs by a blinded expert panel. Eligibility is through the need for a high-risk dental procedure in the mandible where at least 50-Gy radiotherapy has been received. Patients are randomised 1:1 to hyperbaric oxygen arm (Marx protocol) : control arm, but both groups receive antibiotics and chlorhexidine mouthwash. The primary endpoint is the presence of osteoradionecrosis at 6 months following surgery, but secondary endpoints include other time points, acute symptoms and pain, quality of life, and where implants are placed, their successful retention.DiscussionThe protocol presented has evolved through feasibility stages and through analysis of interim data. The classification of osteoradionecrosis has undergone technical refinement to ensure that robust definitions are employed. The HOPON trial is the only multi-centre RCT conducted in this clinical setting despite decades of use of hyperbaric oxygen for the prevention of osteoradionecrosis.Trial registrationEuropean Clinical Trials Database, ID: EudraCT200700622527. First registered on 5 November 2007.
Highlights
Osteoradionecrosis of the mandible is the most common serious complication of radiotherapy for head and neck malignancy
The Hyperbaric Oxygen for the Prevention of Osteoradionecrosis (HOPON) trial is the only multi-centre randomised controlled trial (RCT) conducted in this clinical setting despite decades of use of hyperbaric oxygen for the prevention of osteoradionecrosis
This was required to resolve inconsistencies which arose in cases where very small areas of exposed bone were seen: ‘minor bone spicules’ (MBS) were apparent, which occurred in 19% of patients in this initial analysis
Summary
Several areas of controversy have arisen during the development of the HOPON protocol. This, still exposes patients to the documented risks of hyperbaric pressure, and is by some considered unethical because of the implied issues of safety without any chance of benefit Another approach used 40% oxygen and 60% nitrogen [28] providing an alternative lower ‘dose’ of oxygen treatment and correlation of outcome rather than a true control arm. The unblinded design of the trial and need for extra treatments in the HBO arm introduces an inequality in time between randomisation and surgery for that arm This potential methodological concern means that the time points commence at the time of surgery, rather than the date of randomisation, where it might be argued that only at randomisation are the two groups truly comparable.
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