Non-inferiority Trial of Three Cycles of Zoledronic Acid Versus Percutaneous Thermal Ablation in Osteoid Osteoma
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 16
- 主要终点
- Percentage of decrease in bone pain measured on a visual analog scale (VAS) between baseline and the end of treatment larger or equal to 70%.
研究概览
简要总结
Osteoid osteoma (OO) is a benign osteogenic tumor occurring in children and young adults, responsible for intense bone pain, which has a tendency to spontaneously heal with mineralization of the nidus, but extremely slowly. This healing may be accelerated in patients taking NSAIDs regularly during a few years. The long delay for healing and intense pain, explain why patients are quickly directed to surgeons or specialized radiology departments for tumor ablation. But percutaneous treatment or surgical excision destruction can expose the patient to a substantial risk in terms of neurologic or joint damages, depending on the location. Bisphosphonates treatment may be an effective alternative to percutaneous treatment by accelerating the natural history of OO.
详细描述
Osteoid osteomas (OOs) are small, benign but painful bone tumors, mainly observed in children and young adults. Pain, almost universal, is characteristically greater at night. Pain is well relieved by NSAIDs but resolution is not always complete and pain reappears a few hours after the last dose. Also long-term consumption of NSAID can lead to serious adverse events. Therefore OOs are usually cured shortly after diagnosis, mainly by means of percutaneous treatment (PT) under computed tomography (CT) (radiofrequency coagulation or interstitial laser ablation).
The clinical success rate using these techniques is 96% at 6-month, 94% at 24-month. However, the technique is not distributed everywhere since it is performed by highly specialized interventional radiologists. The PT is performed under general, spinal or regional anesthesia. General anesthesia is used in most cases, especially in children. When the OO is located in close proximity to the skin, cartilage, vessels and nerves, severe complications may occur and additional procedures such as infusion of saline or injection of CO2 at the interface between the OO and the vulnerable structure are done. Also few anatomic locations are not accessible to a PT.
The natural history of OOs remains poorly understood. However investigators in small series of conservatively treated OOs suggested a spontaneous healing of the lesion with mineralization of the nidus and resolution of pain (mean duration of pain in patients with NSAID treatment: 33 months NSAID).
The efficacy of bisphosphonates on pain related to benign (Langherhans cell histiocytosis, fibrous dysplasia, Paget disease) or malignant bone lesions has been widely reported. The investigators observed such efficacy in a small series of 20 patients with percutaneously hard-to-reach or recurrent OO using one to three infusions of zoledronate. The clinical efficacy assessed on pain relief was accompanied by a significantly increased mineralization of the nidus. The investigators postulated that bisphosphonates had accelerated the natural history of OO.
Our hypothesis is that three infusions of zoledronate (4mg) repeated monthly in patients with symptomatic OO is non-inferior to percutaneous treatment on the efficacy, measured by pain relief at Visual Analogical Scale (VAS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age superior or equal to 10 years
- •Patient with a typical osteoid osteoma diagnosed on clinical and radiological criteria (MRI and scanner), validated by a binomial clinician / radiologist.
- •OO never treated or in treatment failure, or recurrent OO.
- •OO percutaneously accessible
- •Pain intensity is superior or equal to 40 mm on a VAS at inclusion visit.
- •Written informed consent signed by the patient or his representative (for minors, agreement of the child and signature of the two mandatory parents).
- •Patient affiliated to the social security.
排除标准
- •Patients with other diseases or receiving treatment that may impact on bone tissue or its metabolism.
- •Patients suffering from renal failure (i.e. lower than 60 ml/min according to the Cowcroft equation).
- •Patients with severe hepatocellular insufficiency (TP<50%).
- •Patients with a history of iritis or uveitis.
- •Patient with untreated rickets or osteomalacia.
- •Patient with untreated dental infection or planed dental surgery during the study period.
- •Patient with untreated infection of the external auditory canal (ex: furuncle, eczema superinfection)
- •Patient already treated by bisphosphonates.
- •Patients with hypersensitivity to the active substance, to other bisphosphonates or to any of the excipients (List of excipients: mannitol (E421), sodium citrate (E331), water for injections).
- •Patient enrolled in another biomedical research protocol and during the whole study
- •Pregnant or breastfeeding women, or planning pregnancy during the course of the study
- •Women of child bearing potential (women following menarche and until post-menopause) and sexually active, without an effective contraceptive measure during the period of treatment (hormonal contraception or mechanical contraception)*
- •* Oral contraceptive methods include:
- •combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravagina or transdermal)
- •progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravagina or transdermal).
- •Mechanical methods of contraception include intrauterine device and intrauterine hormone-releasing system.Patient enrolled in another biomedical research protocol and during the whole study
- •Patients who would not meet the inclusion criteria "OO percutaneously accessible" will be offered to participate in a register, only in Lariboisière hospital. This register will target specifically children aged of at least 12 years old and adults.
研究组 & 干预措施
1: Percutaneous treatment
Percutaneous treatment of OO is a thermal tumor destruction by radiofrequency or laser photocoagulation performed under CT control with strict aseptic approach and most often under general anesthesia. The introductive needle is inserted toward the nidus. Then the optic fiber or the radiofrequency probe is inserted in the nidus center and thermal destruction of the tumor is obtained.When the distance between the nidus and a nerve or the skin is less than 10 mm, infusion of normal saline or CO2 is introduced as spacing agent. When the nidus is in the subchondral bone, cold normal saline is introduced in the joint to protect the cartilage. In addition, a thermocouple is placed in the epidural or foraminal space to continuously monitor the temperature. A procedure typically required between 1 and 2 h from the time the patient entered the CT unit.
干预措施: Thermal destruction with radiofrequency or laser (Device)
2: Bisphosphonate treatment
The treatment consists of 3 infusions of zoledronic acid administered at a monthly interval. Bisphosphonate treatment is considered finished 1 month after the third bisphosphonate infusion (V4 visit). In few cases, the analgesic efficacy provided by 3 bisphosphonate infusions cannot be sufficient: 1 to 3 additional infusions could be proposed to the patient.
Zoledronic acid is supplied as a 4 mg/100 ml solution for infusion. It will be administered as infusion over 30 minutes under the supervision of a nurse. Adults will receive intravenous infusion of 4 mg of zoledronic acid. Children will receive infusion of 0.025 mg/kg of zoledronic acid.
The investigators propose abacus corresponding to zoledronic acid volume to infuse during 30 minutes for children.
干预措施: Acide Zoledronique (Drug)
结局指标
主要结局
Percentage of decrease in bone pain measured on a visual analog scale (VAS) between baseline and the end of treatment larger or equal to 70%.
时间窗: 4 months
Percentage of decrease in bone pain measured on a visual analog scale (VAS) between baseline and the end of treatment larger or equal to 70%. End of treatment is set at one month after the third administration of bisphosphonates and three months after the percutaneous thermal destruction (ie 4 months after inclusion visit = V4 visit, for both groups).
次要结局
- Pain(at 1, 2, 3, 7, 10 and 16 months)
- Patient'Global Impression of change (PGIC)(at 2, 3, 7, 10 and 16 months)
- Consumption of analgesic and NSAIDs(at inclusion, 1, 2, 3, 4, 7, 10 and 16 months)
- Nidus mineralization on CT scan images(4 months)
- Surface of bone marrow edema on MR images(at 4 and 16 months)
- Incidence of Treatment-Emergent Adverse Events of bisphosphonates and percutaneous treatment.(at inclusion, 1, 2, 3, 4, 7, 10 and 16 months)