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
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] 293237 0
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 305281 0
Condition category
Condition code
Injuries and Accidents 304590 304590 0 0
Other injuries and accidents
Neurological 304591 304591 0 0
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] 299495 0
Treatment: Drugs
Comparator / control treatment
100 ml 0.9% Saline every 6 hours for 7 days
Control group
Placebo

Outcomes
Primary outcome [1] 303808 0
Protocol adherence rate assessed by review of medication charts and patient records
Timepoint [1] 303808 0
daily for 7 days
Primary outcome [2] 303827 0
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] 303827 0
daily over the 12 month period of the trial.
Secondary outcome [1] 340207 0
Change in serum concentration of Neuron-Specific Enolase
Timepoint [1] 340207 0
every second day for 7 days
Secondary outcome [2] 340208 0
ICU length of stay assessed by review of patient and ICU records
Timepoint [2] 340208 0
total number of days by day 28.
Secondary outcome [3] 340230 0
Continuous EEG seizure activity (seizure episodes per day)
Timepoint [3] 340230 0
daily for 7 days
Secondary outcome [4] 340312 0
Change in serum concentration of S100B
Timepoint [4] 340312 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
Actual
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)
VIC
Recruitment hospital [1] 9294 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 17959 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 297866 0
Hospital
Name [1] 297866 0
Royal Melbourne Hospital Intensive Care Research Fund
Address [1] 297866 0
Royal Melbourne Hospital
Department of Intensive Care
300 Grattan Street
Parksville, Victoria 3050
Country [1] 297866 0
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] 296911 0
None
Name [1] 296911 0
Address [1] 296911 0
Country [1] 296911 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 298917 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 298917 0
Office for Research
Level 2
South West
300 Grattan Street
Parkville, Victoria, 3050
Ethics committee country [1] 298917 0
Australia
Date submitted for ethics approval [1] 298917 0
29/11/2017
Approval date [1] 298917 0
Ethics approval number [1] 298917 0

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 78638 0
Dr Adam Deane
Address 78638 0
Royal Melbourne Hospital
Department of Intensive Care
Level 6
B Building
300 Grattan Street
Parkville, Victoria, 3050
Country 78638 0
Australia
Phone 78638 0
+61 3 9342 9100
Fax 78638 0
Email 78638 0
adam.deane.mh.org.au
Contact person for public queries
Name 78639 0
Dr Adam Deane
Address 78639 0
Royal Melbourne Hospital
Department of Intensive Care
Level 6
B Building
300 Grattan Street
Parkville, Victoria, 3050
Country 78639 0
Australia
Phone 78639 0
+61 3 9342 9100
Fax 78639 0
Email 78639 0
adam.deane@mh.org.au
Contact person for scientific queries
Name 78640 0
Dr Robert McNamara
Address 78640 0
Royal Melbourne Hospital
Department of Intensive Care
Level 6
B Building
300 Grattan Street
Parkville, Victoria, 3050
Country 78640 0
Australia
Phone 78640 0
+61427534453
Fax 78640 0
Email 78640 0
robert.mcnamara@mh.org.au

No data has been provided for results reporting
Summary results
Not applicable