Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children-the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial
Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children-the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial
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DOI：
10.1186/s13063-019-3511-4
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发表时间：
2019-07-04
期刊：
影响因子：
2.5
通讯作者：
Irvine, Alan T.
中科院分区：
文献类型：
--
作者：
Hartshorn, Stuart;Barrett, Michael J.;Irvine, Alan T.
背景受伤引起的疼痛是去急诊科 (ED) 的儿童最常见的症状之一，而在院前和急诊室中，这种疼痛往往没有得到充分的治疗，部分原因是持续评估和易于使用的镇痛方案的可用性存在挑战。因此，疼痛实践是一个关键的研究重点，包括儿科急诊医学领域。甲氧氟烷通过自行给药的 Penthrox (R) 吸入器输送，属于氟化烃类挥发性麻醉剂，在低剂量下具有镇痛特性，是该类药物中独一无二的。尽管临床急性镇痛使用已有 30 多年的历史，并且有大量证据支持其安全性和有效性，但 Penthrox (R) 的随机对照试验数据仍然很少。方法这是一项国际多中心随机、双盲、安慰剂对照 III 期试验，评估通过 Penthrox (R) 吸入器输送甲氧氟烷用于治疗儿童和青少年中度至重度急性创伤性疼痛的有效性和安全性6-17岁。在签署书面知情同意书后，符合条件的参与者被随机分配自行吸入甲氧氟烷（最大剂量 2x3ml）或生理盐水安慰剂（最大剂量 2x5ml）。患者、治疗临床医生和研究护士对治疗不知情。主要结果是治疗开始后 15 分钟时疼痛强度的变化，通过视觉模拟量表 (VAS) 或 Wong-Baker FACES (R) 疼痛评定量表测量，后者转换为 VAS 值。次要结局指标包括 VAS 评分较基线降低 30% 的应答者人数和比例、所需的救援药物、首次缓解疼痛的时间和吸入次数、患者、临床医生和研究护士的总体用药表现评估，以及治疗期间和随后 142 天期间经历的不良事件的评估。主要分析将按意向治疗进行。每个治疗组的总样本量为 110 名随机接受治疗的患者。讨论儿科损伤的甲氧氟烷镇痛 (MAGPIE) 试验将为通过 Penthrox (R) 吸入器给药的甲氧氟烷在患有中度至重度损伤相关疼痛的儿童和青少年中提供疗效和安全性数据。试验注册EudraCT，2016-004290-41。于 2017 年 4 月 11 日注册。ClinicalTrials.gov，NCT03215056。注册日期：2017 年 7 月 12 日。
BackgroundPain from injuries is one of the commonest symptoms in children attending emergency departments (EDs), and this is often inadequately treated in both the pre-hospital and ED settings, in part due to challenges of continual assessment and availability of easily administered analgesic options. Pain practices are therefore a key research priority, including within the field of paediatric emergency medicine. Methoxyflurane, delivered via a self-administered Penthrox (R) inhaler, belongs to the fluorinated hydrocarbon group of volatile anaesthetics and is unique among the group in having analgesic properties at low doses. Despite over 30years of clinical acute analgesia use, and a large volume of evidence supporting its safety and efficacy, there is a paucity of randomised controlled trial data for Penthrox (R).MethodsThis is an international multi-centre randomised, double-blind, placebo-controlled phase III trial assessing the efficacy and safety of methoxyflurane delivered via the Penthrox (R) inhaler for the management of moderate to severe acute traumatic pain in children and young people aged 6-17years. Following written informed consent, eligible participants are randomised to self-administer either inhaled methoxyflurane (maximum dose of 2x3ml) or normal saline placebo (maximum dose 2x5ml). Patients, treating clinicians and research nurses are blinded to the treatment. The primary outcome is the change in pain intensity at 15min after the commencement of treatment, as measured by the Visual Analogue Scale (VAS) or the Wong-Baker FACES (R) Pain Rating scale, with the latter converted to VAS values. Secondary outcome measures include the number and proportion of responders who achieve a 30% reduction in VAS score compared to baseline, rescue medication requested, time and number of inhalations to first pain relief, global medication performance assessment by the patient, clinician and research nurse, and evaluation of adverse events experienced during treatment and during the subsequent 142days. The primary analysis will be by intention to treat. The total sample size is 110 randomised and treated patients per treatment arm.DiscussionThe Methoxyflurane AnalGesia for Paediatric InjuriEs (MAGPIE) trial will provide efficacy and safety data for methoxyflurane administered via the Penthrox (R) inhaler, in children and adolescents who present to EDs with moderate to severe injury-related pain.Trial registrationEudraCT, 2016-004290-41. Registered on 11 April 2017. ClinicalTrials.gov, NCT03215056. Registered on 12 July 2017.