Delirium, Hematopoietic Stem Cell Transplantation, Thiamine Deficiency
Conditions
Brief summary
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.
Detailed description
Delirium is a common and potentially preventable neuropsychiatric complication in cancer patients receiving hematopoietic stem cell transplantation (HSCT) that has profound consequences. Among cancer patients hospitalized for HSCT, delirium occurs in approximately 40% of patients and increases the risk of mortality. Long-term, delirium in this population results in worse physical health, mental health, and quality of life. Though strategies to prevent delirium have the potential to significantly improve the lives of people living with cancer, research in this area is extremely limited. Thiamine deficiency is also ubiquitous during HSCT and a known contributor to the development of delirium in other patient populations. High dose intravenous (IV) thiamine is an evidence-based and promising treatment for delirium, but no one has studied IV thiamine as a prevention strategy. This is a randomized double-blind controlled trial in participants undergoing allogeneic HSCT to determine if high dose IV thiamine can prevent delirium and minimize the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and other neuropsychiatric outcomes. The investigators will recruit 60 patients admitted for allogeneic HSCT at UNC, randomize them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluate all participants for delirium and related comorbidities. The investigators will use the Delirium Rating Scale (DRS) to measure the severity and duration of delirium immediately prior to transplant and after HSCT until 30 days post-transplant or discharge. If delirium is identified, the DRS will be administered daily until delirium resolves. The investigators will obtain thiamine levels and other laboratory parameters associated with delirium the day after transplant, and continue to monitor thiamine levels weekly thereafter. The investigators will also monitor HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to transplant and at one, three, and six months after transplant to elucidate the persistent impact of delirium in this population and the potential for thiamine to mitigate these negative outcomes.
Interventions
DRUGThiamine
200 mg IV three times daily for seven days
DRUGNormal saline
Normal saline IV three times daily for seven days
Sponsors
Rising Tide Foundation
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admission to the UNC Hospital Bone Marrow Transplant Unit for allogeneic stem cell transplant * At least 18 years of age * Able to speak English * Able to provide informed consent
Exclusion criteria
* A history of adverse reaction to IV thiamine * Pregnancy, confirmed by a negative pregnancy test within 30 days of study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Delirium | 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 least one assessment with DRS \> 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delirium Duration | 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 number of consecutive days during which DRS \> 12. |
| Concentration of Thiamine Status Stratified by Delirium Status | 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. |
| Change in Health-related Quality of Life Scores (Month 1) | 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. |
| Change in Health-related Quality of Life Scores (Month 3) | 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. |
| Change in Health-related Quality of Life Scores (Month 6) | 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. |
| Change in Depression Scores (Month 1) | 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. |
| Change in Depression Scores (Month 3) | 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. |
| Change in Depression Scores (Month 6) | 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. |
| Delirium Severity | 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 reported for each group at baseline and in each week of hospitalization for thiamine and placebo groups. |
| Change in Post-traumatic Stress Symptom Scores (Month 3) | 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. |
| Change in Post-traumatic Stress Symptom Scores (Month 6) | Baseline to six 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. |
| Change in Cognitive Function Scores (Month 1) | From baseline to one month post-transplant | Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time. |
| Change in Cognitive Function Scores (Month 3) | Baseline to three months post-transplant | Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time. |
| Change in Cognitive Function Scores (Month 6) | From baseline to six months post-transplant | Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time. |
| Change in Functional Status Scores (Month 1) | Baseline to one month post-transplant | Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time. |
| Change in Functional Status Scores (Month 3) | From baseline to three months post-transplant | Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time. |
| Change in Functional Status Scores (Month 6) | Baseline to six months post-transplant | Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time. |
| Change in Post-traumatic Stress Symptom Scores (Month 1) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the UNC Bone Marrow Transplant and Cellular Therapies Unit from October 2017 through February 2020.
Pre-assignment details
Of the 66 participants who enrolled in the study, 2 withdrew prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Thiamine 200 mg IV
Thiamine: 200 mg IV three times daily for seven days | 28 |
| Control Normal saline IV
Normal saline: Normal saline IV three times daily for seven days | 33 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1-month Follow-Up | Lost to Follow-up | 1 | 0 |
| 3-month Follow-Up | Lost to Follow-up | 1 | 3 |
| 6-month Follow-Up | Lost to Follow-up | 2 | 2 |
| Inpatient Phase | Death | 1 | 0 |
| Inpatient Phase | Inadequate Drug Exposure | 0 | 1 |
| Inpatient Phase | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Intervention | Control | Total |
|---|---|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 12.5 | 53.6 years STANDARD_DEVIATION 14.7 | 54.2 years STANDARD_DEVIATION 13.6 |
| CIBMTR Disease Risk Index high | 5 Participants | 2 Participants | 7 Participants |
| CIBMTR Disease Risk Index intermediate | 3 Participants | 9 Participants | 12 Participants |
| CIBMTR Disease Risk Index low | 17 Participants | 19 Participants | 36 Participants |
| CIBMTR Disease Risk Index N/A | 3 Participants | 3 Participants | 6 Participants |
| Conditioning Regimen Myeloablative | 15 Participants | 13 Participants | 28 Participants |
| Conditioning Regimen Reduced Intensity or Non-Myeloablative | 13 Participants | 20 Participants | 33 Participants |
| Diagnosis Acute leukemia | 18 Participants | 19 Participants | 37 Participants |
| Diagnosis Chronic leukemia | 2 Participants | 5 Participants | 7 Participants |
| Diagnosis Lymphoma | 0 Participants | 2 Participants | 2 Participants |
| Diagnosis Myelodysplastic Syndrome | 5 Participants | 5 Participants | 10 Participants |
| Diagnosis Myeloproliferative Disorder | 2 Participants | 1 Participants | 3 Participants |
| Diagnosis Other | 1 Participants | 1 Participants | 2 Participants |
| Donor Type Haploidentical | 3 Participants | 5 Participants | 8 Participants |
| Donor Type Matched Related Donor | 9 Participants | 10 Participants | 19 Participants |
| Donor Type Matched Unrelated Donor | 16 Participants | 18 Participants | 34 Participants |
| ECOG Score 0 | 13 Participants | 18 Participants | 31 Participants |
| ECOG Score 1 | 15 Participants | 14 Participants | 29 Participants |
| ECOG Score 2 | 0 Participants | 1 Participants | 1 Participants |
| Education | 14.7 years STANDARD_DEVIATION 2.7 | 15.3 years STANDARD_DEVIATION 2.7 | 15.0 years STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 32 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 27 Participants | 52 Participants |
| Region of Enrollment United States | 28 participants | 33 participants | 61 participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 0 / 34 |
| other Total, other adverse events | 0 / 30 | 0 / 34 |
| serious Total, serious adverse events | 0 / 30 | 0 / 34 |
Outcome results
Primary
Percentage of Participants With Delirium
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 least one assessment with DRS \> 12.
Time frame: 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.
Population: The analysis population was defined a priori as those participants who: 1.) received at least 17 of 21 (80%) scheduled study drug doses; 2.) received at least one dose on each of the study drug administration days; and 3.) had no fewer than one DRS assessment per week until they were found to be delirious, reached 30 days post-transplant, or were discharged.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Percentage of Participants With Delirium | 25 percentage of participants |
| Control | Percentage of Participants With Delirium | 21 percentage of participants |
Secondary
Change in Cognitive Function Scores (Month 1)
Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.
Time frame: From baseline to one month post-transplant
Population: One participant in the control arm was unable to complete the MoCA due to restrictions on in-person human subjects research during the COVID-19 pandemic. Otherwise, all participants available at the 1-month follow-up time point were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Cognitive Function Scores (Month 1) | -0.70 score on a scale | Standard Deviation 3.35 |
| Control | Change in Cognitive Function Scores (Month 1) | -0.09 score on a scale | Standard Deviation 2.76 |
Secondary
Change in Cognitive Function Scores (Month 3)
Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.
Time frame: Baseline to three months post-transplant
Population: Participants who completed the 3 month follow-up period and we able to participate in the cognitive assessment. Of the 26 participants active in the thiamine arm at the 3 month follow-up, 1 did not complete this measure due to barriers related to the COVID-19 pandemic.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Cognitive Function Scores (Month 3) | -0.12 score on a scale | Standard Deviation 0.97 |
| Control | Change in Cognitive Function Scores (Month 3) | 0.97 score on a scale | Standard Deviation 2.82 |
Secondary
Change in Cognitive Function Scores (Month 6)
Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.
Time frame: From baseline to six months post-transplant
Population: Participants who completed the 6 month follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Cognitive Function Scores (Month 6) | 0.71 score on a scale | Standard Deviation 3.32 |
| Control | Change in Cognitive Function Scores (Month 6) | 1.54 score on a scale | Standard Deviation 2.87 |
Secondary
Change in Depression Scores (Month 1)
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.
Time frame: Baseline to one month post-transplant
Population: Participants who completed the 1 month follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Depression Scores (Month 1) | -1.34 T-score | Standard Deviation 8.28 |
| Control | Change in Depression Scores (Month 1) | 1.16 T-score | Standard Deviation 6.12 |
Secondary
Change in Depression Scores (Month 3)
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.
Time frame: Baseline to three months post-transplant
Population: Participants who completed the 3 month follow-up period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Depression Scores (Month 3) | 0.93 T-score | Standard Deviation 6.24 |
| Control | Change in Depression Scores (Month 3) | 0.32 T-score | Standard Deviation 9.53 |
Secondary
Change in Depression Scores (Month 6)
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.
Time frame: Baseline to six months post-transplant
Population: Participants who completed the 6 month follow-up period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Depression Scores (Month 6) | 0.14 T-score | Standard Deviation 6.88 |
| Control | Change in Depression Scores (Month 6) | -1.66 T-score | Standard Deviation 7.89 |
Secondary
Change in Functional Status Scores (Month 1)
Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.
Time frame: Baseline to one month post-transplant
Population: Participants who completed the 1 month follow-up period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Functional Status Scores (Month 1) | 0.70 score on a scale | Standard Deviation 0.67 |
| Control | Change in Functional Status Scores (Month 1) | 0.88 score on a scale | Standard Deviation 0.93 |
Secondary
Change in Functional Status Scores (Month 3)
Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.
Time frame: From baseline to three months post-transplant
Population: Participants who completed the 3 month follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Functional Status Scores (Month 3) | 0.69 score on a scale | Standard Deviation 0.62 |
| Control | Change in Functional Status Scores (Month 3) | 0.60 score on a scale | Standard Deviation 0.89 |
Secondary
Change in Functional Status Scores (Month 6)
Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.
Time frame: Baseline to six months post-transplant
Population: Participants who completed the 6 month follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Functional Status Scores (Month 6) | 0.46 score on a scale | Standard Deviation 0.93 |
| Control | Change in Functional Status Scores (Month 6) | 0.21 score on a scale | Standard Deviation 0.63 |
Secondary
Change in Health-related Quality of Life Scores (Month 1)
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.
Time frame: From baseline to one month post-transplant
Population: Participants who completed the 1 month follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Health-related Quality of Life Scores (Month 1) | -7.53 score on a scale | Standard Deviation 11.66 |
| Control | Change in Health-related Quality of Life Scores (Month 1) | -5.69 score on a scale | Standard Deviation 11.59 |
Secondary
Change in Health-related Quality of Life Scores (Month 3)
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.
Time frame: Baseline to three months post-transplant
Population: Participants who completed the 3 month follow-up period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Health-related Quality of Life Scores (Month 3) | -3.96 score on a scale | Standard Deviation 9.11 |
| Control | Change in Health-related Quality of Life Scores (Month 3) | -1.43 score on a scale | Standard Deviation 16.79 |
Secondary
Change in Health-related Quality of Life Scores (Month 6)
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.
Time frame: Baseline to six months post-transplant
Population: Participants who completed the 6 month follow-up period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Health-related Quality of Life Scores (Month 6) | -4.36 score on a scale | Standard Deviation 14.09 |
| Control | Change in Health-related Quality of Life Scores (Month 6) | 0.28 score on a scale | Standard Deviation 12.17 |
Secondary
Change in Post-traumatic Stress Symptom Scores (Month 1)
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.
Time frame: Baseline to one month post-transplant
Population: Participants who completed the 1 month follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Post-traumatic Stress Symptom Scores (Month 1) | -0.52 score on a scale | Standard Deviation 10.88 |
| Control | Change in Post-traumatic Stress Symptom Scores (Month 1) | 1.55 score on a scale | Standard Deviation 6.92 |
Secondary
Change in Post-traumatic Stress Symptom Scores (Month 3)
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.
Time frame: Baseline to three months post-transplant
Population: Participants who completed the 3 month follow-up period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Post-traumatic Stress Symptom Scores (Month 3) | -1.50 score on a scale | Standard Deviation 6.58 |
| Control | Change in Post-traumatic Stress Symptom Scores (Month 3) | 0.83 score on a scale | Standard Deviation 5.63 |
Secondary
Change in Post-traumatic Stress Symptom Scores (Month 6)
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.
Time frame: Baseline to six months post-transplant
Population: Participants who completed the 6 month follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Post-traumatic Stress Symptom Scores (Month 6) | 1.79 score on a scale | Standard Deviation 9.14 |
| Control | Change in Post-traumatic Stress Symptom Scores (Month 6) | 1.32 score on a scale | Standard Deviation 7 |
Secondary
Concentration of Thiamine Status Stratified by Delirium Status
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.
Time frame: 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
Population: Only those participants in whom thiamine levels were obtained at the end of the seven day administration were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Concentration of Thiamine Status Stratified by Delirium Status | 115.6 nmol/L | Standard Deviation 69.3 |
| Control | Concentration of Thiamine Status Stratified by Delirium Status | 93.8 nmol/L | Standard Deviation 28.5 |
Secondary
Delirium Duration
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 number of consecutive days during which DRS \> 12.
Time frame: 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.
Population: These analyses are exclusive to those participants who experienced delirium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Delirium Duration | 2.0 days | Standard Deviation 1.2 |
| Control | Delirium Duration | 4.4 days | Standard Deviation 4.7 |
Secondary
Delirium Severity
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 reported for each group at baseline and in each week of hospitalization for thiamine and placebo groups.
Time frame: 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
Population: Attrition over time is due to hospital discharge (primary reason), withdrawal, or death.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intervention | Delirium Severity | Week 3 | 6.33 score on a scale |
| Intervention | Delirium Severity | Baseline | 4.0 score on a scale |
| Intervention | Delirium Severity | Week 4 | 5.50 score on a scale |
| Intervention | Delirium Severity | Week 2 | 6.50 score on a scale |
| Intervention | Delirium Severity | Week 5 | 20.00 score on a scale |
| Intervention | Delirium Severity | Week 1 | 4.83 score on a scale |
| Control | Delirium Severity | Week 5 | 7.50 score on a scale |
| Control | Delirium Severity | Week 1 | 4.67 score on a scale |
| Control | Delirium Severity | Week 2 | 5.33 score on a scale |
| Control | Delirium Severity | Week 3 | 5.17 score on a scale |
| Control | Delirium Severity | Week 4 | 6.00 score on a scale |
| Control | Delirium Severity | Baseline | 4.0 score on a scale |