Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000589684
Ethics application status
Approved
Date submitted
2/05/2023
Date registered
30/05/2023
Date last updated
30/05/2023
Date data sharing statement initially provided
30/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
How much thiamine is enough in malnourished patients receiving total parenteral nutrition?
Scientific title
Thiamine levels and duration of replacement in patients receiving total parenteral nutrition (TPN) with moderate to severe risk of refeeding - a prospective randomised controlled trial
Secondary ID [1] 309577 0
None
Universal Trial Number (UTN)
Trial acronym
TIE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malnutrition 329881 0
Total parenteral nutrition 329882 0
Thiamine deficiency 329883 0
Condition category
Condition code
Diet and Nutrition 326786 326786 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Thiamine replacement (b dose forte brand) 250mg daily intravenously for 7 days
Intervention code [1] 326005 0
Treatment: Drugs
Comparator / control treatment
Comparator group will be 3 days replacement of thiamine (250mg b dose forte intravenously)
Control group
Active

Outcomes
Primary outcome [1] 334639 0
Thiamine blood levels (whole blood thiamine - thiamine diphosphate (TDP)
Timepoint [1] 334639 0
At day 3 and 7 post enrolment
Secondary outcome [1] 421492 0
Economic evaluation comparing cost of two approaches (3 and 7 days) incorporating administration/nursing time, as well as drug costs.
Cost and time data will be sourced from trial hospital pharmacy, and time will be estimated by observing nursing staff administering the medication.
Timepoint [1] 421492 0
Day 7 following enrolment

Eligibility
Key inclusion criteria
Receiving total parenteral nutrition
Ability to consent to participate or surrogate decision maker available
Refeeding risk classified as moderate or severe as per 2020 American Society of Parenteral and Enteral Nutrition (ASPEN) refeeding syndrome guideline.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Not at risk of re-feeding
Unable to consent.
Duration of TPN expected to be less than 7 days.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central computer generated randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Crossover is possible, if thiamine levels are low at day 3, to crossover to 7 days of replenishment.
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Descriptive summaries of patient demographic data will consist of frequency distributions for categorical variables and means (SD) or medians (IQR) for continuous variables. Univariate comparisons between groups will be done using Chi-squared or Fisher Exact tests for categorical data and t-tests or Mann-Whitney U tests for continuous data. Proportions of non-deficiency will be compared between groups at baseline and days 3 and 7 using Chi-squared tests and Generalised linear mixed models (GLMM). Results will be summarised using odds ratios and 95% confidence intervals. LMM with random subject effects will be used to compare raw thiamine levels between groups at baseline and days 3 and 7. Results will be summarised using estimated means and 95% confidence intervals. Cost differences between groups will be described using means (SD) and compared using t tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/05/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
65
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 24664 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 40275 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 313765 0
Hospital
Name [1] 313765 0
Charlies Foundation for Research
Country [1] 313765 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue
Nedlands 6009 WA
Country
Australia
Secondary sponsor category [1] 315592 0
None
Name [1] 315592 0
Address [1] 315592 0
Country [1] 315592 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312933 0
Sir Charles Gairdner and Osborne Park Hospital Ethics Committee
Ethics committee address [1] 312933 0
Hospital Avenue
Nedlands WA 6009
Ethics committee country [1] 312933 0
Australia
Date submitted for ethics approval [1] 312933 0
Approval date [1] 312933 0
30/09/2020
Ethics approval number [1] 312933 0
03911

Summary
Brief summary
Thiamine deficiency manifests as two conditions: cardiac (wet) beriberi, or Wernicke’s encephalopathy. Furthermore, it can potentiate lactic acidosis through failure of pyruvate to enter the Kreb’s cycle.

Patients who are malnourished are at risk of thiamine deficiency, and traditionally, replacement is given for patients at risk (patients on TPN without micronutrients, those with history of alcohol abuse, starvation states). Thiamine levels are not routinely checked in usual practice, but instead, supplementation is provided based on risk.
The current guidelines give different recommendations (excluding for treatment of beriberi/Wernicke’s, in which the dose is 200-500mg intravenously three times a day for 5-7 days followed by 100mg for 1-2 weeks)
1. For those at high risk of thiamine deficiency, therapeutic guidelines suggests giving 300mg intravenously for 3 days and then 100mg daily for 1-2 weeks
2. In re-feeding syndrome 100mg intravenously for 7-10 days



Clinical Question

Is 3 days of intravenous thiamine replacement in patients receiving TPN AND at risk of refeeding syndrome, sufficient to restore and maintain thiamine levels when measured at day 7?

Hypothesis
In patients at risk of refeeding syndrome, thiamine levels are sufficiently restored with 3 days, as opposed to 7 days, of supplementation.

Methodology

Patients randomized to receive 3 days of intravenous thiamine or 7 days of intravenous thiamine.
Standard dose will be given, 250mg b dose forte intravenous.

Thiamine levels will be measured at day 0, 3 and 7 to ensure adequate blood levels are reached.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126390 0
A/Prof Matthew Anstey
Address 126390 0
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands 6009, WA
Country 126390 0
Australia
Phone 126390 0
+61 8 64571010
Fax 126390 0
Email 126390 0
matthew.anstey@health.wa.gov.au
Contact person for public queries
Name 126391 0
A/Prof Matthew Anstey
Address 126391 0
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands 6009, WA
Country 126391 0
Australia
Phone 126391 0
+61 8 64571010
Fax 126391 0
Email 126391 0
matthew.anstey@health.wa.gov.au
Contact person for scientific queries
Name 126392 0
A/Prof Matthew Anstey
Address 126392 0
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands 6009, WA
Country 126392 0
Australia
Phone 126392 0
+61 8 64571010
Fax 126392 0
Email 126392 0
matthew.anstey@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data dictionaries can be shared.

De-identified patient level data
When will data be available (start and end dates)?
At the completion of the trial. Available for 5 years after publication.
Available to whom?
Researchers on reasonable request.
Available for what types of analyses?
Meta-analyses
How or where can data be obtained?
On reasonable request to the PI via email (matthew.anstey@health.wa.gov.au) . Will need to obtain ethics approval as well for any data sharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.