Department of Haematology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.
Comprehensive Clinical Trials Unit at UCL, London, UK.
Trials. 2018 Jan 22;19(1):55. doi: 10.1186/s13063-017-2419-0.
In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life.
METHODS/DESIGN: Eligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90% for < 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI). Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8-11, 12-15, 16-22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use. For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist. The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment.
Altering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events.
ISRCTN46012373 . Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015 Sponsor: University Hospital Southampton. Sponsor's protocol code: RHMCHIOT53.
除了疼痛，镰状细胞贫血（HbSS）并发症还包括与夜间和白天低氧饱和度相关的注意力和处理速度的神经认知障碍，这些问题因阻塞性睡眠呼吸暂停（OSA）而变得更加复杂。在普通人群中，OSA 采用持续气道正压通气（CPAP）治疗。本单盲、随机、对照二期试验的目的是比较自动调节 CPAP（APAP）与标准护理在 HbSS 个体中的疗效，以确定该干预措施是否能改善注意力和处理速度、大脑结构、疼痛和生活质量。
方法/设计：入选标准包括：有能力提供知情同意；年龄>8 岁；HbSS 诊断；夜间氧饱和度<90%的时间>30%（即不符合当前夜间吸氧治疗标准）。主要排除标准是：夜间呼吸支持；呼吸或失代偿性心力衰竭；慢性输血；或 APAP 治疗或磁共振成像（MRI）禁忌证。将 60 名 HbSS 患者（30 名儿童和 30 名成人）随机分为标准治疗+APAP 组或标准治疗组，治疗时间为 6 个月。最小化因素为：年龄组（8-11、12-15、16-22 和>23 岁）；MRI 上有静默性梗死；最低夜间氧饱和度>90%或<90%；以及羟基脲的使用。对于 APAP 个体，干预措施在家中进行。通过记录每晚使用时间和夜间血氧饱和度的软件来记录依从性和效果。未设盲的睡眠生理学家通过提供合适的面罩和促进依从性来为参与者提供支持。主要结局是韦氏量表的删除子测验的变化。次要结局包括一般认知功能、定量脑 MRI、血液和尿液化学、生活质量和通过智能手机应用程序（GoMedSolutions，Inc）记录的日常疼痛（GoMedSolutions，Inc），以及在可能的情况下通过 MRI 心脏、超声心动图和 6 分钟步行测试评估。这些结果将由不了解治疗分配的评估者在基线和治疗 6 个月时进行评估。
改变 HbSS 中的氧饱和度可能导致骨髓抑制。通过在基线、两周、三个月和六个月时监测全血细胞计数，提供适当的治疗，并报告为安全事件，可以降低这种风险。
ISRCTN46012373。于 2015 年 7 月 10 日注册。方案版本：6.0 日期：2015 年 12 月 24 日主办方：南安普敦大学医院。主办方方案代码：RHMCHIOT53。
