Department of Endocrinology, Alder Hey Children's NHS Foundation Trust, Liverpool L12 2AP, UK
Clinical Trials Research Centre, University of Liverpool, Liverpool, UK.
BMJ. 2019 Apr 3;365:l1226. doi: 10.1136/bmj.l1226.
To compare the efficacy, safety, and cost utility of continuous subcutaneous insulin infusion (CSII) with multiple daily injection (MDI) regimens during the first year following diagnosis of type 1 diabetes in children and young people.
Pragmatic, multicentre, open label, parallel group, randomised controlled trial and economic evaluation.
15 paediatric National Health Service (NHS) diabetes services in England and Wales. The study opened to recruitment in May 2011 and closed in January 2017.
Patients aged between 7 months and 15 years, with a new diagnosis of type 1 diabetes were eligible to participate. Patients who had a sibling with the disease, and those who took drug treatments or had additional diagnoses that could have affected glycaemic control were ineligible.
Participants were randomised, stratified by age and treating centre, to start treatment with CSII or MDI within 14 days of diagnosis. Starting doses of aspart (CSII and MDI) and glargine or detemir (MDI) were calculated according to weight and age, and titrated according to blood glucose measurements and according to local clinical practice.
Primary outcome was glycaemic control (as measured by glycated haemoglobin; HbA1c) at 12 months. Secondary outcomes were percentage of patients in each treatment arm with HbA1c within the national target range, incidence of severe hypoglycaemia and diabetic ketoacidosis, change in height and body mass index (as measured by standard deviation scores), insulin requirements (units/kg/day), partial remission rate (insulin dose adjusted HbA1c <9), paediatric quality of life inventory score, and cost utility based on the incremental cost per quality adjusted life year (QALY) gained from an NHS costing perspective.
294 participants were randomised and 293 included in intention to treat analyses (CSI, n=144; MDI, n=149). At 12 months, mean HbA1c was comparable with clinically unimportant differences between CSII and MDI participants (60.9 mmol/mol 58.5 mmol/mol, mean difference 2.4 mmol/mol (95% confidence interval -0.4 to 5.3), P=0.09). Achievement of HbA1c lower than 58 mmol/mol was low among the two groups (66/143 (46%) CSII participants 78/142 (55%) MDI participants; relative risk 0.84 (95% confidence interval 0.67 to 1.06)). Incidence of severe hypoglycaemia and diabetic ketoacidosis were low in both groups. Fifty four non-serious and 14 serious adverse events were reported during CSII treatment, and 17 non-serious and eight serious adverse events during MDI treatment. Parents (but not children) reported superior PedsQL scores for those patients treated with CSII compared to those treated with MDI. CSII was more expensive than MDI by £1863 (€2179; $2474; 95% confidence interval £1620 to £2137) per patient, with no additional QALY gains (difference -0.006 (95% confidence interval -0.031 to 0.018)).
During the first year following type 1 diabetes diagnosis, no clinical benefit of CSII over MDI was identified in children and young people in the UK setting, and treatment with either regimen was suboptimal in achieving HbA1c thresholds. CSII was not cost effective.
Current Controlled Trials ISRCTN29255275; European Clinical Trials Database 2010-023792-25.
比较儿童和青少年在确诊 1 型糖尿病后的第一年中，连续皮下胰岛素输注（CSII）与多次皮下胰岛素注射（MDI）方案在疗效、安全性和成本效用方面的差异。
实用、多中心、开放标签、平行组、随机对照试验和经济评估。
英格兰和威尔士的 15 家 NHS 儿科糖尿病服务机构。研究于 2011 年 5 月开始招募，于 2017 年 1 月结束。
年龄在 7 个月至 15 岁之间、新诊断为 1 型糖尿病的患者有资格参加。有兄弟姐妹患有该疾病的患者，以及正在接受药物治疗或有其他可能影响血糖控制的额外诊断的患者不符合条件。
参与者在确诊后 14 天内，按年龄和治疗中心分层，随机分配开始接受 CSII 或 MDI 治疗。门冬氨酸（CSII 和 MDI）和甘精或地特胰岛素（MDI）的起始剂量根据体重和年龄计算，并根据血糖测量结果和当地临床实践进行滴定。
主要结局是 12 个月时的血糖控制（以糖化血红蛋白表示；HbA1c）。次要结局包括每个治疗组中 HbA1c 在国家目标范围内的患者比例、严重低血糖和糖尿病酮症酸中毒的发生率、身高和体重指数（以标准偏差分数表示）的变化、胰岛素需求（单位/公斤/天）、部分缓解率（调整后的胰岛素剂量 HbA1c<9）、儿科生活质量量表评分，以及从 NHS 成本角度基于增量成本每获得一个质量调整生命年（QALY）的成本效用。
共有 294 名参与者被随机分组，293 名参与者纳入意向治疗分析（CSII，n=144；MDI，n=149）。在 12 个月时，CSII 和 MDI 组参与者的 HbA1c 具有临床无重要差异（60.9mmol/mol vs. 58.5mmol/mol，平均差异 2.4mmol/mol[95%置信区间 -0.4 至 5.3]，P=0.09）。两组中达到 HbA1c 低于 58mmol/mol 的比例都较低（CSII 组 66/143（46%）；MDI 组 78/142（55%）；相对风险 0.84[95%置信区间 0.67 至 1.06]）。两组的严重低血糖和糖尿病酮症酸中毒发生率均较低。CSII 治疗期间报告了 54 例非严重和 14 例严重不良事件，MDI 治疗期间报告了 17 例非严重和 8 例严重不良事件。与 MDI 治疗相比，父母（而非儿童）报告 CSII 治疗的患者的 PedsQL 评分更高。CSII 比 MDI 每例患者多花费 £1863（€2179；$2474；95%置信区间 £1620 至 £2137），但没有额外的 QALY 获益（差异 -0.006（95%置信区间 -0.031 至 0.018））。
在英国儿童和青少年中，确诊 1 型糖尿病后的第一年中，CSII 与 MDI 相比没有显示出临床优势，两种治疗方案在达到 HbA1c 阈值方面都不理想。CSII 没有成本效益。
当前对照试验 ISRCTN85422167；欧洲临床试验数据库 2010-023792-25。
