A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation

Abstract

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.

Keywords: Cognitive impairment; Delirium; Hematopoietic stem cell transplantation; Thiamine; Wernicke's encephalopathy; Wernicke-Korsakoff syndrome.

Conflict of interest statement

Competing Interests: Dr. Wood receives funding from Pfizer for research not directly related to this work but that could be perceived to constitute a conflict of interest. Otherwise, the authors have no competing interests to report.

Copyright © 2021 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Study Schema a. Cognition (Montreal Cognitive Assessment, MoCA), Functional Status (Eastern Cooperative Oncology Group Performance Status, ECOG-PS), Depression (Patient Reported Outcome Measurement Information System, PROMIS), Health-related Quality of Life (Functional Assessment of Cancer Therapy – Bone Marrow Transplant, FACT-BMT) b. Thiamine 200 mg IV three times daily vs. Placebo; post-transplantation days 1-7 c. Delirium Rating Scale (DRS) d. Thiamine levels on post-transplantation days 1, 8, 15, 22, 29

Figure 2.

Consort Diagram

Figure 3.

Cumulative incidence of delirium

Figure 4.

Thiamine levels during hospitalization for allogeneic hematopoietic stem cell transplantation

Figure 5.

Thiamine deficiency during hospitalization for allogeneic hematopoietic stem cell transplantation