ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR

Registration number

ACTRN12617001553369p

Ethics application status

Submitted, not yet approved

Date submitted

31/10/2017

Date registered

13/11/2017

Date last updated

20/12/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

The Effect of Intravenous Sodium Ascorbate on Secondary Brain Injury in a Cohort of Severe Traumatic Brain Injury patients: The Orange Concentrate Randomised Control Trial.

Scientific title

A double-blinded pilot randomized control trial comparing the effect of intravenous vitamin C versus placebo on secondary neurological injury in a cohort of severe traumatic brain injury patients.

Secondary ID [1]

none

Universal Trial Number (UTN)

U1111-1204-3877

Trial acronym

Linked study record

Health condition

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

Severe Traumatic Brain Injury

Condition category

Condition code

Injuries and Accidents

Other injuries and accidents

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Arm 1: 3g Sodium Ascorbate in 100 ml 0.9% Saline solution intravenous infusion every 6 hours for 7 days

Arm 2: 6g Sodium Ascorbate in 100 ml 0.9% Saline intravenous infusion every 6 hours for 7 days

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

100 ml 0.9% Saline every 6 hours for 7 days

Control group

Placebo

Outcomes

Primary outcome [1]

Protocol adherence rate assessed by review of medication charts and patient records

Timepoint [1]

daily for 7 days

Primary outcome [2]

Protocol enrolment rate - total number of enrolled patients versus total number of suitable but not enrolled patients admitted to the unit over the 12 month period of study.

Timepoint [2]

daily over the 12 month period of the trial.

Secondary outcome [1]

Change in serum concentration of Neuron-Specific Enolase

Timepoint [1]

every second day for 7 days

Secondary outcome [2]

ICU length of stay assessed by review of patient and ICU records

Timepoint [2]

total number of days by day 28.

Secondary outcome [3]

Continuous EEG seizure activity (seizure episodes per day)

Timepoint [3]

daily for 7 days

Secondary outcome [4]

Change in serum concentration of S100B

Timepoint [4]

every second day for 7 days

Eligibility

Key inclusion criteria

Non-penetrating Severe Traumatic Brain Injury (GCS 8 or lower)
Predicted to require at least 48 hrs of mechanical ventilatory support in ICU.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Chronic Renal Impairment (eGFR less than 90)
Glucose-6-Phosphate Dehydrogenase Deficiency
Current Pregancy
Moribund/not expected to survive for more than 48 hrs

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)

Sealed opaque envelopes

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computerised generated sequence

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 1 / Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Pilot study.
Total enrolment target: 24 (8 in each group)

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

8/01/2018

Actual

Date of last participant enrolment

Anticipated

8/01/2019

Actual

Date of last data collection

Anticipated

14/03/2019

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

3050 - Parkville

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal Melbourne Hospital Intensive Care Research Fund

Address [1]

Royal Melbourne Hospital
Department of Intensive Care
300 Grattan Street
Parksville, Victoria 3050

Country [1]

Australia

Primary sponsor type

Individual

Name

Professor Rinaldo Bellomo

Address

Royal Melbourne Hospital
Department of Intensive Care
300 Grattan Street
Parksville, Victoria 3050

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Melbourne Health Human Research Ethics Committee

Ethics committee address [1]

Office for Research
Level 2
South West
300 Grattan Street
Parkville, Victoria, 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/11/2017

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

In response to the onset of significant inflammatory signalling following severe traumatic brain injury, ascorbate (vitamin C) concentrations rapidly fall to levels associated with severe deficiency.   Without replacement, the ascorbate levels remain reduced for the duration of the inflammatory response.

There is mounting evidence that replacing ascorbate plasma levels during an inflammatory response may be beneficial, particularly to the brain.  Ascorbate is known to be an essential co-factor in several brain metabolic processes.  These processes include reducing oxidative stress, maintaining microcirculatory homeostasis and maintaining normalm function of several key enzyme systems, including endothelial nitric oxide synthase (eNOS).  In addition, ascorbate is involved in brain energy production, and is required for the production of  a significant number of neurotransmitters.  It is clear from multiple animal and human studies that deficiency in ascorbate leads to a pro-inflammatory state and worsening organ failure.  

In response to traumatic brain injury, brain ascorbate levels fall markedly in line with body concentrations.   The magnitude of plasma level ascorbate decrease, which often reaches levels associated with scurvy in critical illness, has been shown to correlate with severity of both neurological injury and more general injury severity.

Ascorbate supplementation has been shown to reduce the severity of secondary brain injury in multiple animal studies.  There is a need to further evaluate the role of intravenous sodium ascorbate in the setting of human brain injury.  To this end the authors propose to conduct a small feasibility study in the Australian setting to establish the efficacy of the proposed intervention and to evaluate the effect of intravenous sodium ascorbate on patients suffering from severe traumatic brain injury.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Adam Deane

Address

Royal Melbourne Hospital
Department of Intensive Care
Level 6
B Building
300 Grattan Street
Parkville, Victoria, 3050

Country

Australia

Phone

+61 3 9342 9100

Fax

adam.deane.mh.org.au

Contact person for public queries

Name

Adam Deane

Address

Royal Melbourne Hospital
Department of Intensive Care
Level 6
B Building
300 Grattan Street
Parkville, Victoria, 3050

Country

Australia

Phone

+61 3 9342 9100

Fax

adam.deane@mh.org.au

Contact person for scientific queries

Name

Robert McNamara

Address

Royal Melbourne Hospital
Department of Intensive Care
Level 6
B Building
300 Grattan Street
Parkville, Victoria, 3050

Country

Australia

Phone

+61427534453

Fax

robert.mcnamara@mh.org.au

No information has been provided regarding IPD availability

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.

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