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Trial registered on ANZCTR


Registration number
ACTRN12620000651987p
Ethics application status
Not yet submitted
Date submitted
14/05/2020
Date registered
5/06/2020
Date last updated
5/06/2020
Date data sharing statement initially provided
5/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of mega-dose Vitamin C for patients with severe infections who are admitted to the intensive care unit
Scientific title
Mega-dose Vitamin C for patients with septic shock: a pilot randomised controlled trial
Secondary ID [1] 301216 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
severe infection 317366 0
Septic shock 317603 0
Condition category
Condition code
Cardiovascular 315474 315474 0 0
Other cardiovascular diseases
Infection 315682 315682 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vitamin C 30 grams [100 ml] diluted with 150 ml of 5% Dextrose infused intravenously over 1 hour followed immediately by Vitamin C 30 grams [100 ml] diluted with 150 ml of 5% Dextrose infused intravenously over 5 hours with monitoring of the fluid administered occurring via audit of the ICU fluid balance chart.
Intervention code [1] 317518 0
Treatment: Drugs
Comparator / control treatment
5% Dextrose 250 ml infused intravenously over 1 hour followed immediately by 5% Dextrose 250 ml infused intravenously over 5 hours with monitoring of the fluid administered occurring via audit of the ICU fluid balance chart.
Control group
Placebo

Outcomes
Primary outcome [1] 323719 0
Urine output volume in millilitres
Timepoint [1] 323719 0
Cumulative urine output for 24 consecutive hours following the beginning of the study treatment infusion as obtained from the participant's electronic fluid balance chart.
Secondary outcome [1] 382716 0
Change of serum sodium levels of equal to or greater than 10 mEq/L
Timepoint [1] 382716 0
During the six-hour study infusion period the baseline serum sodium level along with levels at 1 hour, 4 hours and 6 hours will be assessed via an audit of the the participant's electronic medical record.
Secondary outcome [2] 382940 0
Incidence of absolute serum sodium level greater than 160 mEq/L
Timepoint [2] 382940 0
During the six-hour study infusion period the baseline serum sodium level along with levels at 1 hour, 4 hours and 6 hours will be assessed via an audit of the the participant's electronic medical record.
Secondary outcome [3] 382941 0
Time alive and free of intravenous vasopressor drug support
Timepoint [3] 382941 0
Total time in hours after randomisation for the subsequent 168 consecutive hours (7 days) as obtained from the participant's electronic medical record. Vasopressor drug free is defined as the first time the participant has their vasopressor drugs discontinued for a minimum of 4-consecutive hours, censored at 7 days following commencement of the study drug infusion, as obtained from the participant's electronic medical record.
Secondary outcome [4] 382942 0
Alive and not-admitted to the intensive care unit
Timepoint [4] 382942 0
Number of days alive and discharged from the intensive care unit for 28 days from the day of enrolment as obtained from the participant's electronic medical record.
Secondary outcome [5] 382943 0
Cumulative invasive mechanical ventilation-free hours
Timepoint [5] 382943 0
Total mechanical ventilation-free hours over the 28-day period following randomisation as obtained from the participant's electronic medical record.
Secondary outcome [6] 382944 0
Cumulative length of renal replacement therapy
Timepoint [6] 382944 0
Total renal replacement therapy hours over the 28-day period following randomisation as obtained from the participant's electronic medical record.
Secondary outcome [7] 382945 0
Serum Vitamin C levels
Timepoint [7] 382945 0
Serum blood sample levels of Vitamin C obtained immediately prior to the commencement of the study infusion and at, 1 hour, 4 hours, 6 hours and 24 hours following the commencement of the study infusion.
Secondary outcome [8] 382946 0
Urinary oxalate crystals
Timepoint [8] 382946 0
A single urinary sample measurement obtained from a urine sample obtained 24 hours following the commencement of the study drug infusion.
Secondary outcome [9] 382947 0
Serum Interleukin-6 inflammatory biomarker level
Timepoint [9] 382947 0
Serum blood sample levels of Interleukin-6 obtained from blood samples taken immediately prior to the commencement of the study infusion and at, 1 hour, 4 hours, 6 hours and 24 hours following the commencement of the study infusion.
Secondary outcome [10] 382948 0
Serum tumor necrosis factor biomarker level
Timepoint [10] 382948 0
Serum blood sample levels of Interleukin-6 obtained from blood samples taken immediately prior to the commencement of the study infusion and at, 1 hour, 4 hours, 6 hours and 24 hours following the commencement of the study infusion.
Secondary outcome [11] 382949 0
Serum Interleukin-10 biomarker level
Timepoint [11] 382949 0
Serum blood sample levels of Interleukin-10 obtained from blood samples taken immediately prior to the commencement of the study infusion and at, 1 hour, 4 hours, 6 hours and 24 hours following the commencement of the study infusion.
Secondary outcome [12] 382950 0
intensive care unit mortality
Timepoint [12] 382950 0
Mortality status at time of intensive care unit discharge as obtained from the participant's electronic medical record
Secondary outcome [13] 382951 0
Hospital mortality
Timepoint [13] 382951 0
Mortality status at time of hospital discharge as obtained from the participant's electronic medical record
Secondary outcome [14] 382952 0
Time from eligibility to commence of study drug infusion
Timepoint [14] 382952 0
Time in hours from the positive determination that the participant is eligible, has been enrolled and the study drug infusion has been commenced for fully eligible participants as obtained from the participant's electronic medical record.

Eligibility
Key inclusion criteria
Suspected or confirmed septic shock defined as an acute increase of:
- equal to or greater than 2 sequential organ failure assessment (SOFA) points
- need for continuous intravenous vassopressor therapy to maintain a mean arterial blood pressure of greater than 65 mmHg for greater than 2 hours and a serum lactate of greater than 2 mmol/L (despite adequate fluid resuscitation) within the previous 24 hours.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Aged less than 18 years
Suspected or confirmed pregnancy
Do not resuscitate or do not intubate order
Death is deemed to be imminent or inevitable during this index hospital admission
Patients with know human immunodeficiency virus (HIV) infection
Patients with known glucose-6 phosphate dehydrogenanse (G-6PD) deficiency
Patients transferred from another intensive care unit or hospital with a diagnosis of septic shock for greater than 24 hours
Patient with known chronic iron overload due to iron storage and other diseases
Patient previously enrolled in this study
Patients with chronic haemodialysis or peritoneal dialysis.
Patients require renal replacement therapy within next 24 hours.
Patients baseline blood sodium level is equal to or greater than 160 mEq/L
Patients with known or suspected:
- history of oxalate nephropathy or hyperoxaluria
- short blow syndrome or severe fat malabsorption
- acute beri-beri disease
- acute Wernicke's encephalopathy
- malaria
- scurvy

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)
Permuted block randomisation
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 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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] 16625 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 30220 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 305663 0
Hospital
Name [1] 305663 0
Austin Hospital
Address [1] 305663 0
145 Studley Road
Heidelberg
Victoria 3084
Country [1] 305663 0
Australia
Primary sponsor type
Individual
Name
Professor Rinaldo Bellomo
Address
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country
Australia
Secondary sponsor category [1] 306074 0
Hospital
Name [1] 306074 0
Austin Health
Address [1] 306074 0
145 Studley Road
Heidelberg
Victoria 3084
Country [1] 306074 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 305948 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 305948 0
c/o Office for Research
Level 8, Harold Stokes Building
145 Studley Road
Heidelberg
Victoria 3084
Ethics committee country [1] 305948 0
Australia
Date submitted for ethics approval [1] 305948 0
27/05/2020
Approval date [1] 305948 0
Ethics approval number [1] 305948 0

Summary
Brief summary
Septic shock, which is a state of severe infection, triggers a complex response by the body (the inflammatory response) that causes a decrease in blood pressure and subsequently one or more organ systems to fail when blood supply to these organs is reduced.

When patients are admitted to intensive care with sepsis and/or septic shock they receive a range of therapies including antibiotics, intravenous fluids and strong drugs to improve blood pressure, known as vasopressor drugs.. However, these therapies have significant side effects and it would be desirable to restore a safe blood pressure quickly.

Over the last few years, evidence has emerged that high dose Vitamin C administered via infusion may help to restore blood pressure with almost no side effects. This makes treatment with Vitamin C potentially desirable in patients with on-going low-blood pressure due to septic shock. However, this effect might be dose dependent and we do not know the effect of mega dose Vitamin C.

In response, we will perform a clinical research project, known as a randomised controlled trial, to evaluate whether giving intravenous mega-dose Vitamin C (total of 60 grams) compared to placebo, improves physiological outcomes in a population of 30 patients admitted to intensive care with a diagnosis of suspected or confirmed sepsis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102170 0
Prof Rinaldo Bellomo
Address 102170 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 102170 0
Australia
Phone 102170 0
+61 3 9496 5992
Fax 102170 0
+61 3 9496 3932
Email 102170 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 102171 0
Dr Glenn Eastwood
Address 102171 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 102171 0
Australia
Phone 102171 0
+61 3 9496 4835
Fax 102171 0
+61 3 9496 3932
Email 102171 0
glenn.eastwood@austin.org.au
Contact person for scientific queries
Name 102172 0
Prof Rinaldo Bellomo
Address 102172 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 102172 0
Australia
Phone 102172 0
+61 3 9496 5992
Fax 102172 0
+61 3 9496 3932
Email 102172 0
rinaldo.bellomo@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 7951 0
Study protocol
Citation [1] 7951 0
Link [1] 7951 0
Email [1] 7951 0
rinaldo.bellomo@austin.org.au
Other [1] 7951 0
Attachment [1] 7951 0
Summary results
No Results