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NCT03263442

High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation

Completed Phase 2 Results posted Last updated 19 October 2021
What this trial tests

Phase 2 trial testing Thiamine in Hematopoietic Stem Cell Transplantation in 66 participants. Completed in 10 August 2020.

Timeline
16 October 2017
Primary endpoint
2 March 2020
10 August 2020

Quick facts

Lead sponsorUNC Lineberger Comprehensive Cancer Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment66
Start date16 October 2017
Primary completion2 March 2020
Estimated completion10 August 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

UNC Lineberger Comprehensive Cancer Center — full company profile →

Who can join

18 and older, any sex, with Hematopoietic Stem Cell Transplantation or Delirium. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Delirium Primary · Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.

Delirium incidence will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium incidence will be defined as at

GroupValue95% CI
Intervention25
Control21
Delirium Severity Secondary · Assessments will occur in the week prior to transplant (baseline), then at least 3 times post-transplant on a weekly basis until 30 days post-transplant or discharge, whichever comes first, up to week 5

Delirium severity will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The score ranges from 0 to 32 with higher scores reflecting more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. The DRS medians and ranges are report

Baseline
GroupValue95% CI
Intervention4.02.0 – 8.0
Control4.02.0 – 7.0
Week 1
GroupValue95% CI
Intervention4.833.0 – 9.0
Control4.672.67 – 15.00
Week 2
GroupValue95% CI
Intervention6.502.67 – 20.33
Control5.332.33 – 16.00
Week 3
GroupValue95% CI
Intervention6.331.00 – 18.60
Control5.172.00 – 17.80
Week 4
GroupValue95% CI
Intervention5.504.00 – 20.00
Control6.005.00 – 13.50
Week 5
GroupValue95% CI
Intervention20.0020.00 – 20.00
Control7.504.00 – 8.00
Delirium Duration Secondary · Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.

Delirium duration will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium duration will be reported as num

GroupValue95% CI
Intervention2.0± 1.2
Control4.4± 4.7
Concentration of Thiamine Status Stratified by Delirium Status Secondary · From end of 7-day intervention period until the development of delirium at any point during the post-transplant hospitalization up to a maximum of 30 days

The relationship between thiamine levels at the end of the seven day administration of thiamine and the development of delirium at any point during the thirty days post-transplant or the post-transplant hospitalization, whichever comes first, will be examined. Thiamine levels (nmol/L) are presented in participants who did and did not experience delirium.

GroupValue95% CI
Delirium115.6± 69.3
No Delirium93.8± 28.5
Change in Health-related Quality of Life Scores (Month 1) Secondary · From baseline to one month post-transplant

HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

GroupValue95% CI
Intervention-7.53± 11.66
Control-5.69± 11.59
Change in Health-related Quality of Life Scores (Month 3) Secondary · Baseline to three months post-transplant

HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

GroupValue95% CI
Intervention-3.96± 9.11
Control-1.43± 16.79
Change in Health-related Quality of Life Scores (Month 6) Secondary · Baseline to six months post-transplant

HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

GroupValue95% CI
Intervention-4.36± 14.09
Control0.28± 12.17
Change in Depression Scores (Month 1) Secondary · Baseline to one month post-transplant

Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

GroupValue95% CI
Intervention-1.34± 8.28
Control1.16± 6.12
Change in Depression Scores (Month 3) Secondary · Baseline to three months post-transplant

Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

GroupValue95% CI
Intervention0.93± 6.24
Control0.32± 9.53
Change in Depression Scores (Month 6) Secondary · Baseline to six months post-transplant

Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

GroupValue95% CI
Intervention0.14± 6.88
Control-1.66± 7.89
Change in Post-traumatic Stress Symptom Scores (Month 1) Secondary · Baseline to one month post-transplant

Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

GroupValue95% CI
Intervention-0.52± 10.88
Control1.55± 6.92
Change in Post-traumatic Stress Symptom Scores (Month 3) Secondary · Baseline to three months post-transplant

Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

GroupValue95% CI
Intervention-1.50± 6.58
Control0.83± 5.63

Sponsor's own description

Purpose: To conduct a randomized controlled pilot study investigating the use of high dose intravenous (IV) thiamine to prevent delirium and mitigate the long-term effects of delirium, including health-related quality of life (HRQOL), functional status, and neuropsychiatric outcomes, in patients admitted to University of North Carolina (UNC) Hospital for allogeneic hematopoietic stem cell transplant (HSCT). Participants: 60 adult inpatients admitted to the UNC Bone Marrow Transplant Unit for allogeneic stem cell transplant. Procedures (methods): Participants will be admitted for allogeneic HSCT and on the day after transplant randomized to seven days of high dose IV thiamine or placebo. Thiamine levels will be measured weekly and participants will be assessed for evidence of delirium using validated measures. Validated measures will also be used to assess cognitive function, depression, post-traumatic stress symptoms, functional status, and HRQOL prior to hospitalization and at one, three, and six months after transplant.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cognitive function in patients prior to undergoing allogeneic hematopoietic stem cell transplantation.
    Nakamura ZM, Deal AM, Rosenstein DL, Quillen LJ, et al · · 2021 · cited 9× · PMID 32829465 · DOI 10.1007/s00520-020-05697-2
  2. Delirium in Critical Illness Patients and the Potential Role of Thiamine Therapy in Prevention and Treatment: Findings from a Scoping Review with Implications for Evidence-Based Practice.
    Lange S, Mędrzycka-Dąbrowska W, Friganovic A, Oomen B, et al · · 2021 · cited 8× · PMID 34444556 · DOI 10.3390/ijerph18168809
  3. A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation.
    Nakamura ZM, Deal AM, Park EM, Quillen LJ, et al · · 2021 · cited 4× · PMID 33945982 · DOI 10.1016/j.jpsychores.2021.110503
  4. Impact of patient and clinical characteristics on cognitive changes after allogeneic hematopoietic stem cell transplantation.
    Nakamura ZM, Heiling HM, Park EM, Deal AM, et al · · 2021 · cited 3× · PMID 34601501 · DOI 10.1038/s41409-021-01481-w
  5. Design of a randomized placebo controlled trial of high dose intravenous thiamine for the prevention of delirium in allogeneic hematopoietic stem cell transplantation.
    Nakamura ZM, Deal AM, Rosenstein DL, Quillen LJ, et al · · 2020 · cited 1× · PMID 32619524 · DOI 10.1016/j.cct.2020.106076

Verify or expand the search:

Other trials of Thiamine

Trials testing the same drug.

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Trials by the same sponsor.

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