一项维生素 D 缺乏危重症患儿（VITdAL-PICU 研究）中胆钙化醇的 II 期剂量评估、可行性、随机对照试验。

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

机构信息

Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.

Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.

出版信息

BMC Pediatr. 2023 Aug 14;23(1):397. doi: 10.1186/s12887-023-04205-9.

DOI:10.1186/s12887-023-04205-9

PMID:37580663

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10424361/

Abstract

BACKGROUND

Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.

METHODS

We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.

RESULTS

Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).

CONCLUSIONS

A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.

CLINICALTRIALS

gov NCT02452762 Registered 25/05/2015.

摘要

背景

维生素 D 缺乏症（VDD）在儿科重症监护病房（ICU）中非常普遍，并且与更差的临床病程有关。成人 ICU 的试验表明，使用肠内负荷剂量快速恢复维生素 D 状态是安全的，并且可能改善结局。在儿科 ICU 中，尚未发表关于 VDD 快速正常化的试验。

方法

我们于 2016 年至 2017 年进行了一项多中心、安慰剂对照的 II 期可行性随机临床试验。我们使用 2:1 的随机分组比，将来自加拿大、智利和奥地利 ICU 的 67 名患有 VDD 的危重症儿童随机分为接受肠内胆钙化醇（10,000 IU/kg，最大 400,000 IU）负荷剂量或安慰剂的组。参与者、护理人员和结局评估人员均为盲法。主要目的是确定负荷剂量是否能使维生素 D 状态正常化（25（OH）D>75 nmol/L）。次要目标是评估不良事件并评估 III 期试验的可行性。

结果

在 67 名随机参与者中，有 1 名退出，7 名在方案修改为单次负荷剂量之前接受了超过 1 次胆钙化醇治疗，59 名参与者（40 名治疗组，19 名安慰剂组）纳入主要分析。治疗组 31/38（81.6%）名参与者的血浆 25（OH）D 浓度>75 nmol/L，而安慰剂组 1/18（5.6%）名。治疗组的平均 25（OH）D 浓度为 125.9 nmol/L（SD 63.4）。没有证据表明维生素 D 毒性，也没有发生主要药物或安全方案违规事件。入组率为 3.4 例/月，支持更大规模试验的可行性。84%的患者在第 7 天采集了血液样本。对 40 名参与家庭进行的一项调查显示，健康相关生活质量（HRQL）是家庭对主要试验（30，75%）最重要的结果。