Objective

To determine if high dose intravenous (IV) thiamine can prevent delirium during hospitalization following allogeneic HSCT. Secondarily, we evaluated the effects of high dose IV thiamine on thiamine levels and explored risk factors for delirium.

Methods

Randomized, double-blind, placebo-controlled trial in patients undergoing allogeneic HSCT at a U.S. academic medical center between October 2017 and March 2020. 64 participants were randomized 1:1 to thiamine 200 mg IV three times daily for 7 days or placebo. We used the Delirium Rating Scale to assess for delirium. Delirium incidence was compared between groups using the chi-square test. Group differences in time to onset and duration of delirium were compared using the Kaplan-Meier method. Fisher's Exact and Wilcoxon Rank Sum tests were used to examine associations between pre-transplantation variables and delirium.

Results

61 participants were analyzed. Delirium incidence (25% vs. 21%, Chi-square (df = 1) = 0.12, p = 0.73), time to onset, duration, and severity were not different between study arms. Immediately following the intervention, thiamine levels were higher in the thiamine arm (275 vs. 73 nmol/L, t-test (df = 57) = 13.63, p < 0.0001), but not predictive of delirium. Variables associated with delirium in our sample included disease severity, corticosteroid exposure, infection, and pre-transplantation markers of nutrition.

Conclusion

High dose IV thiamine did not prevent delirium in patients receiving allogeneic HSCT. Given the multiple contributors to delirium in this population, further research regarding the efficacy of multicomponent interventions may be needed.

Trial Registration: Clinical Trials NCT03263442.

Funding: Rising Tide Foundation for Clinical Cancer Research.

中文翻译：

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静脉注射硫胺素预防异基因造血干细胞移植后谵妄的随机双盲安慰剂对照试验

客观的

确定高剂量静脉注射 (IV) 硫胺素是否可以预防异基因 HSCT 后住院期间的谵妄。其次，我们评估了高剂量静脉注射硫胺素对硫胺素水平的影响，并探讨了谵妄的危险因素。

方法

2017 年 10 月至 2020 年 3 月期间在美国学术医疗中心对接受异基因 HSCT 的患者进行的随机、双盲、安慰剂对照试验。64 名参与者以 1:1 的比例随机分配至硫胺素 200 mg 静脉注射，每天 3 次，持续 7 天或安慰剂。我们使用谵妄评定量表来评估谵妄。使用卡方检验比较组间谵妄发生率。使用 Kaplan-Meier 方法比较谵妄发作时间和持续时间的组间差异。Fisher 精确和 Wilcoxon 秩和检验用于检查移植前变量与谵妄之间的关联。

结果

对 61 名参与者进行了分析。谵妄发生率（25% 对 21%，卡方 (df = 1) = 0.12，p  = 0.73）、发病时间、持续时间和严重程度在研究组之间没有差异。干预后立即，硫胺素组的硫胺素水平较高（275 vs. 73 nmol/L，t检验 (df = 57) = 13.63，p  < 0.0001），但不能预测谵妄。我们样本中与谵妄相关的变量包括疾病严重程度、皮质类固醇暴露、感染和移植前营养标志物。

结论

接受同种异体 HSCT 的患者接受高剂量 IV 硫胺素并不能预防谵妄。鉴于该人群中谵妄的多种原因，可能需要进一步研究多组分干预的功效。

试验注册：临床试验 NCT03263442。

资金来源：临床癌症研究 Rising Tide Foundation。