Shaw Richard, Butterworth Christopher, Tesfaye Binyam, Bickerstaff Matthew, Dodd Susanna, Smerdon Gary, Chauhan Seema, Brennan Peter, Webster Keith, McCaul James, Nixon Peter, Kanatas Anastasios, Silcocks Paul
CRUK Liverpool Cancer Trials Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool and Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
CRUK Liverpool Cancer Trials Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Trials. 2018 Jan 10;19(1):22. doi: 10.1186/s13063-017-2376-7.
Osteoradionecrosis 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/DESIGN: The 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.
The 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.
European Clinical Trials Database, ID: EudraCT200700622527 . First registered on 5 November 2007.
下颌骨放射性骨坏死是头颈部恶性肿瘤放疗最常见的严重并发症。几十年来，高压氧一直被用于预防因拔牙或植入种植体而引发的放射性骨坏死病例。使用高压氧的证据仍然不足，目前的临床实践差异很大。我们描述了一项临床试验方案，以评估高压氧在预防放疗后下颌骨手术中放射性骨坏死的益处。
方法/设计：HOPON试验是一项III期随机对照多中心试验。它采用非盲试验设计，但主要终点（即放射性骨坏死的诊断）由一个盲法专家小组根据匿名临床照片和X光片进行评估。入选标准是需要在下颌骨进行高风险牙科手术，且已接受至少50 Gy的放疗。患者按1:1随机分为高压氧组（马克思方案）和对照组，但两组均接受抗生素和洗必泰漱口水治疗。主要终点是术后6个月时是否存在放射性骨坏死，次要终点包括其他时间点、急性症状和疼痛、生活质量，以及在植入种植体的情况下，种植体的成功留存情况。
所提出的方案是通过可行性阶段并对中期数据进行分析而制定的。放射性骨坏死的分类经过了技术改进，以确保采用可靠的定义。尽管高压氧用于预防放射性骨坏死已有数十年，但HOPON试验是在这种临床环境中进行的唯一一项多中心随机对照试验。
欧洲临床试验数据库，ID：EudraCT200700622527。首次注册于2007年11月5日。
