ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12620000651987

Ethics application status

Approved

Date submitted

14/05/2020

Date registered

5/06/2020

Date last updated

21/07/2022

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

severe infection

Septic shock

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Infection

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]

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]

Urine output volume in millilitres

Timepoint [1]

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]

Change of serum sodium levels of equal to or greater than 10 mEq/L

Timepoint [1]

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]

Incidence of absolute serum sodium level greater than 160 mEq/L

Timepoint [2]

Secondary outcome [3]

Time alive and free of intravenous vasopressor drug support

Timepoint [3]

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]

Alive and not-admitted to the intensive care unit

Timepoint [4]

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]

Cumulative invasive mechanical ventilation-free hours

Timepoint [5]

Total mechanical ventilation-free hours over the 28-day period following randomisation as obtained from the participant's electronic medical record.

Secondary outcome [6]

Cumulative length of renal replacement therapy

Timepoint [6]

Total renal replacement therapy hours over the 28-day period following randomisation as obtained from the participant's electronic medical record.

Secondary outcome [7]

Serum Vitamin C levels

Timepoint [7]

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]

Urinary oxalate crystals

Timepoint [8]

A single urinary sample measurement obtained from a urine sample obtained 24 hours following the commencement of the study drug infusion.

Secondary outcome [9]

Serum Interleukin-6 inflammatory biomarker level

Timepoint [9]

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]

Serum tumor necrosis factor biomarker level

Timepoint [10]

Secondary outcome [11]

Serum Interleukin-10 biomarker level

Timepoint [11]

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]

intensive care unit mortality

Timepoint [12]

Mortality status at time of intensive care unit discharge as obtained from the participant's electronic medical record

Secondary outcome [13]

Hospital mortality

Timepoint [13]

Mortality status at time of hospital discharge as obtained from the participant's electronic medical record

Secondary outcome [14]

Time from eligibility to commence of study drug infusion

Timepoint [14]

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

Sex

Both males and females

Can healthy volunteers participate?

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 155 mEq/L
Patients creatinine at enrolment is equal to or greater than 150 mmol/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

Recruiting

Date of first participant enrolment

Anticipated

1/10/2020

Actual

28/10/2020

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]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Austin Hospital

Address [1]

145 Studley Road
Heidelberg
Victoria 3084

Country [1]

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]

Hospital

Name [1]

Austin Health

Address [1]

145 Studley Road
Heidelberg
Victoria 3084

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

c/o Office for Research
Level 8, Harold Stokes Building
145 Studley Road
Heidelberg 
Victoria 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/05/2020

Approval date [1]

17/09/2020

Ethics approval number [1]

HREC/64579/Austin-2020

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

Prof Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

[email protected]

Contact person for public queries

Name

Glenn Eastwood

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 4835

Fax

+61 3 9496 3932

[email protected]

Contact person for scientific queries

Name

Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
7951	Study protocol			[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Targeting oxidative stress in septic acute kidney injury: From theory to practice.	2021	https://dx.doi.org/10.3390/jcm10173798
Embase	Update on vitamin C administration in critical illness.	2022	https://dx.doi.org/10.1097/MCC.0000000000000951
Embase	Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.	2023	https://dx.doi.org/10.1186/s13054-023-04644-x

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically