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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12623000589684

Ethics application status

Approved

Date submitted

2/05/2023

Date registered

30/05/2023

Date last updated

8/12/2024

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]

None

Universal Trial Number (UTN)

Trial acronym

TIE

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Malnutrition

Total parenteral nutrition

Thiamine deficiency

Condition category

Condition code

Diet and Nutrition

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]

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]

Thiamine blood levels (whole blood thiamine - thiamine diphosphate (TDP)

Timepoint [1]

At day 3 and 7 post enrolment

Secondary outcome [1]

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]

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?

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

Recruiting

Date of first participant enrolment

Anticipated

31/05/2023

Actual

15/06/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Sir Charles Gairdner Hospital - Nedlands

Recruitment postcode(s) [1]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Charlies Foundation for Research

Address [1]

Hospital Avenue Nedlands 6009, WA

Country [1]

Australia

Primary sponsor type

Hospital

Name

Sir Charles Gairdner Hospital

Address

Hospital Avenue
Nedlands 6009 WA

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sir Charles Gairdner and Osborne Park Hospital Ethics Committee

Ethics committee address [1]

Hospital Avenue
Nedlands WA 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

30/09/2020

Ethics approval number [1]

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

A/Prof Matthew Anstey

Address

Sir Charles Gairdner Hospital Hospital Avenue Nedlands 6009, WA

Country

Australia

Phone

+61 8 64571010

Fax

[email protected]

Contact person for public queries

Name

Matthew Anstey

Address

Sir Charles Gairdner Hospital Hospital Avenue Nedlands 6009, WA

Country

Australia

Phone

+61 8 64571010

Fax

[email protected]

Contact person for scientific queries

Name

Matthew Anstey

Address

Sir Charles Gairdner Hospital Hospital Avenue Nedlands 6009, WA

Country

Australia

Phone

+61 8 64571010

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

Yes

Will there be any conditions when requesting access to individual participant data?

Persons/groups eligible to request access:
• Researchers on reasonable request.

Conditions for requesting access:
• -

What individual participant data might be shared?

• Data dictionaries can be shared.

De-identified patient level data

What types of analyses could be done with individual participant data?

• Meta-analyses

When can requests for individual participant data be made (start and end dates)?

From:
At the completion of the trial. Available for 5 years after publication.

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?

• On reasonable request to the PI via email ([email protected]) . Will need to obtain ethics approval as well for any data sharing

Are there extra considerations when requesting access to individual participant data?

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.

Trial Review

Documents added manually

Documents added automatically