Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000909123
Ethics application status
Approved
Date submitted
21/06/2019
Date registered
28/06/2019
Date last updated
12/07/2021
Date data sharing statement initially provided
28/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot clinical study of Vitamin C for the prevention of acute kidney injury in critically ill patients
Scientific title
Vitamin C for prevention of acute kidney injury in high-risk critically ill patients: a pilot randomized controlled trial study
Secondary ID [1] 298566 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
kidney injury
 313400 0
Condition category
Condition code
Renal and Urogenital 311833 311833 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Loading of intravenous Vitamin C 30 mg (diluted in 5% DW 250 ml) infused at 15 gm (125 ml) over 1 hour followed by intravenous Vitamin C 15 gm (125 ml) infused over 5 hours).
Followed by intravenous Vitamin C 1500 mg (diluted in 5% DW 100ml) infused over 1 hour administered every 6 hours.
The study treatment will be given every six hours until:
- For a maximum of 72 hours (3 days) OR
- Receiving renal replacement therapy OR
- The patient is discharged from ICU OR
- Patient dies
- The patient develops a complication which may be related to the study drug
(whichever occurs first)
Intervention code [1] 314819 0
Prevention
Comparator / control treatment
Loading of intravenous 5% Dextrose Water 250 ml infused at 125 ml over 1 hour followed by intravenous 125 ml infused over 5 hours).
Followed by intravenous 5% Dextrose Water 100 ml infused over 1 hour administered every 6 hours.

The study treatment will be given every six hours until:
- For a maximum of 72 hours (3 days) OR
- Receiving renal replacement therapy OR
- The patient is discharged from ICU OR
- Patient dies
- The patient develops a complication which may be related to the study drug
(whichever occurs first)
Control group
Placebo

Outcomes
Primary outcome [1] 320505 0
Peak plasma creatinine
Timepoint [1] 320505 0
72 hours after randomization
Secondary outcome [1] 371832 0
Eligibility to screened patient ratio
Timepoint [1] 371832 0
Monthly review of existing electronic patient medical records
Secondary outcome [2] 371833 0
Protocol compliance
Timepoint [2] 371833 0
Review of enrolled patient medication administration charts while the patient is receiving continuous renal replacement therapy and is admitted to the intensive care unit
Secondary outcome [3] 371834 0
Major adverse kidney event at 30 days (known as MAKE30) which defined as the composite of death, use of renal replacement therapy, or persistence of renal dysfunction (defined by serum creatinine being equal to or greater than 200 per cent of reference)
Timepoint [3] 371834 0
Evaluated by electronic medical record serum biochemistry results review at hospital discharge truncated at 30 days.
Secondary outcome [4] 371835 0
Hospital mortality
Timepoint [4] 371835 0
Alive or dead status of patient at hospital discharge as determined by a review of the existing patient medical record.
Secondary outcome [5] 371836 0
Intensive care unit admission duration as assessed via an audit of the existing hospital electronic medical record
Timepoint [5] 371836 0
Number of days in intensive care unit during the admission in which the patient was enrolled.
Secondary outcome [6] 371837 0
Hospital admission duration via an audit of the existing hospital electronic medical record
Timepoint [6] 371837 0
Number of days in hospital during the admission in which the patient was enrolled.
Secondary outcome [7] 371838 0
Duration of vasopressor therapy
Timepoint [7] 371838 0
Number of hours of vasopressor therapy administered from the time of commencement of the study drug infusion during the intensive care unit admission as obtained from a review of the intensive care unit fluid balance chart.
Secondary outcome [8] 371839 0
Hours of renal replacement therapy
Timepoint [8] 371839 0
Number of hours of renal replacement therapy administered from the time of commencement of the study drug infusion during the intensive care unit admission as obtained from a review of the intensive care unit fluid balance chart.
Secondary outcome [9] 371840 0
Cumulative fluid balance at 72 hours following study drug infusion commencement
Timepoint [9] 371840 0
Cumulative fluid balance from the commencement of the study drug infusion during the intensive care unit admission as obtained from a review of the intensive care unit fluid balance chart.

Eligibility
Key inclusion criteria
Within first 24 hours of intensive care unit admission
NephroCheck urine test positive result which is defined as a value exceeding more than 2 ng per ml / 1000.
No evidence of acute kidney dysfunction on intensive care unit admission defined as a serum creatinine measured being less than 150 mircomol/L
No chronic kidney disease defined by the stage II or greater using the Kidney Disease Improving Global Outcomes classification
Are expected to stay in the ICU at least until the day after tomorrow.
Use of indwelling urinary catheter as standard care expected for at least 72 hours after enrolment
At least one of the following acute conditions within 24 hours prior to enrolment, which define clinical high-risk of AKI
Respiratory Sequential Organ Failure Assessment (SOFA) score of equal to or greater than 2 (PaO2/FiO2 < 300)
OR
Cardiovascular SOFA score of equal to or greater than 1 (Mean arterial pressure less than 70 mmHg and/or any vasopressor required)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnancy
DNR (do not resuscitate) DNI (do not intubate) orders
Death is deemed imminent or inevitable during this admission, and either the attending physician, patient or substitute decision-maker is not committed to active treatment
Already receiving dialysis (either acute or chronic) or imminent need of dialysis at the time of enrolment
Known moderate to severe AKI prior to enrolment (KDIGO stage II or greater)
Receiving kidney transplantation
Any other illness that, in the investigator’s judgement, will substantially increase the risk associated with patient's participation in this study
Patients with known HIV infection
Patients with known or suspected history of oxalate nephropathy or hyperoxaluria, scurvy, chronic iron overload, G-6PD deficiency
Clinician expects to prescribe high dose vitamin C for another indications
Patients with known haemochromatosis.

Study design
Purpose of the study
Prevention
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 blocks of variable size.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
Data analysis will be performed on an intention-to-treat basis. Summary statistics will be used to describe the clinical data and presented as mean ± SD, median with interquartile range (IQR) or percentages as appropriate. Chi-squared analysis with Fisher’s exact test (when appropriate), and Student’s t-test (Mann Whitney U test for non-normal distributions) will be used to compare data between the active treatment group and the control group with statistical significance declared for probability values of 0.05 or less. Analysis of the outcome of excluded patients due to other trials etc. will be in accordance with the CONSORT guidelines.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/08/2019
Actual
19/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
17
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14054 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 26844 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 303105 0
Hospital
Name [1] 303105 0
Austin Hospital
Country [1] 303105 0
Australia
Primary sponsor type
Individual
Name
Professor Rinaldo Bellomo
Address
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country
Australia
Secondary sponsor category [1] 303097 0
None
Name [1] 303097 0
Address [1] 303097 0
Country [1] 303097 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303650 0
Austin Hospital Human Research Ethics Committee
Ethics committee address [1] 303650 0
Office for Research
Level 8, Harold Stokes Building,
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Ethics committee country [1] 303650 0
Australia
Date submitted for ethics approval [1] 303650 0
22/03/2019
Approval date [1] 303650 0
02/07/2019
Ethics approval number [1] 303650 0

Summary
Brief summary
Acute kidney injury (AKI) is a medical term that defines a condition when kidneys fail to make enough urine output or dispose of waste products leading to increased level of toxins in blood. AKI effects close to one-third of patients admitted to the intensive care unit (ICU). AKI is problematic as it makes patient care more difficult and exposes such patients to extra risks. This is because patients cannot remove drugs and toxins effectively and cannot control fluids, potassium, and blood acidity in a normal way. AKI, therefore, increases risk of death, and prolongs ICU and hospital length of stay. Unfortunately, despite numerous efforts, no effective treatment to prevent AKI has been developed. One of the reasons for this is that it is difficult to find out which patients are going to develop AKI early enough to intervene. However, there has been recent progressed in this area. A new urine test has been developed called NephroCheck, which measures proteins in the urine that are released when the kidneys are under stress. If such protein levels are high, then these patients are very likely to develop AKI in the next 24 hours. This means that early treatments to can be applied.

Recently, there has been much research regarding the possibility that, in ICU patients, high dose vitamin C, given into through a vein, can protect organs (including the kidney) from malfunctioning in the setting of stress, as occurs in critically ill ICU patients. Such treatment is very safe and has not been reported to cause any side effects so far. It is unknown whether intervening early, in response to the findings of positive NephroCheck test, can prevent the development of AKI. However, the consensus view of the Austin hospital ICU treating team is that, in light of the available evidence, the introduction of such vitamin C therapy is both safe and desirable in ICU and should be studied.

In response, we plan to perform a study to test whether giving high dose vitamin C to patients who have a high risk of developing AKI as identified by positive NephroCheck test can decrease the occurrence and/or intensity of AKI.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94398 0
Prof Rinaldo Bellomo
Address 94398 0
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 94398 0
Australia
Phone 94398 0
+61 3 9496 5992
Fax 94398 0
+61 3 9496 3932
Email 94398 0
[email protected]
Contact person for public queries
Name 94399 0
Prof Rinaldo Bellomo
Address 94399 0
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 94399 0
Australia
Phone 94399 0
+61 3 9496 5992
Fax 94399 0
+61 3 9496 3932
Email 94399 0
[email protected]
Contact person for scientific queries
Name 94400 0
Prof Rinaldo Bellomo
Address 94400 0
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 94400 0
Australia
Phone 94400 0
+61 3 9496 5992
Fax 94400 0
+61 3 9496 3932
Email 94400 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Policy for department no yet finalised


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.