Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

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 details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04796636




Registration number
NCT04796636
Ethics application status
Date submitted
19/01/2021
Date registered
15/03/2021
Date last updated
4/11/2022

Titles & IDs
Public title
High-dose Intravenous Vitamin C in Patients With Septic Shock
Scientific title
HIGH-dose Intravenous VItamin C in Patients With Septic Shock: HIGH-VIS Trial
Secondary ID [1] 0 0
2021.026
Universal Trial Number (UTN)
Trial acronym
HIGH-VIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis, Severe 0 0
Septic Shock 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Infection 0 0 0 0
Studies of infection and infectious agents
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sodium Ascorbate

Experimental: Intermediate dose - Sodium ascorbate (vitamin C) is provided by the manufacturer (Orthomolecular Medisearch Laboratory P/L, Braeside, Victoria, Australia) as 30 grams in 100 ml.
30 gram load over 2 hours (T = 0 - 2 hours)
30 gram infusion over 6 hours (T = 2-8 hours) which will be repeated at 14, 26 and 38 hours

Experimental: High dose - Sodium ascorbate (vitamin C) is provided by the manufacturer (Orthomolecular Medisearch Laboratory P/L, Braeside, Victoria, Australia) as 30 grams in 100 ml.
30 gram load over 2 hours (T = 0 - 2 hours)
60 gram infusion over 6 hours (T = 2-8 hours) which will be repeated at 14, 26 and 38 hours

No Intervention: Usual care - Usual care for septic shock. No vitamin C will be given


Treatment: Drugs: Sodium Ascorbate
As previously described
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to cessation of vasopressor support
Timepoint [1] 0 0
7 days
Secondary outcome [1] 0 0
Plasma C-reactive protein
Timepoint [1] 0 0
24, 48 and 72 hours
Secondary outcome [2] 0 0
Plasma procalcitonin
Timepoint [2] 0 0
24, 48 and 72 hours
Secondary outcome [3] 0 0
Plasma thrombomodulin
Timepoint [3] 0 0
24, 48 and 72 hours
Secondary outcome [4] 0 0
Inflammatory markers
Timepoint [4] 0 0
24, 48 and 72 hours
Secondary outcome [5] 0 0
Body temperature
Timepoint [5] 0 0
24, 48 and 72 hours
Secondary outcome [6] 0 0
Sequential Organ Failure Assessment score
Timepoint [6] 0 0
7 days
Secondary outcome [7] 0 0
Cardiovascular Sequential organ failure assessment score
Timepoint [7] 0 0
7 days
Secondary outcome [8] 0 0
Neurological Sequential organ failure assessment score
Timepoint [8] 0 0
7 days
Secondary outcome [9] 0 0
Haematological Sequential organ failure assessment score
Timepoint [9] 0 0
7 days
Secondary outcome [10] 0 0
Liver Sequential organ failure assessment score
Timepoint [10] 0 0
7 days
Secondary outcome [11] 0 0
Renal Sequential organ failure assessment score
Timepoint [11] 0 0
7 days
Secondary outcome [12] 0 0
Respiratory Sequential organ failure assessment score
Timepoint [12] 0 0
7 days
Secondary outcome [13] 0 0
Maximum plasma concentration of vitamin C (cMax)
Timepoint [13] 0 0
72 hours
Secondary outcome [14] 0 0
Area under the vitamin C plasma concentration versus time curve
Timepoint [14] 0 0
72 hours
Secondary outcome [15] 0 0
Vitamin C plasma elimination half-life
Timepoint [15] 0 0
72 hours
Secondary outcome [16] 0 0
Urinary markers of renal injury
Timepoint [16] 0 0
72 hours
Secondary outcome [17] 0 0
Plasma cystatin C
Timepoint [17] 0 0
72 hours
Secondary outcome [18] 0 0
Plasma proteomics
Timepoint [18] 0 0
72 hours
Secondary outcome [19] 0 0
Number of patients screened
Timepoint [19] 0 0
Duration of study: 12 months
Secondary outcome [20] 0 0
Randomised to screened patient ratio
Timepoint [20] 0 0
Duration of study: 12 months
Secondary outcome [21] 0 0
Percentage of randomized patients compliant with study protocol
Timepoint [21] 0 0
Duration of study: 12 months

Eligibility
Key inclusion criteria
- Diagnosis of septic shock within 24 hours of admission to the ICU

- Age 18 - 80 years

- Presence of a central venous catheter for vasopressor infusion

- Presence of an arterial line to monitor blood pressure

Definition of sepsis Suspected or documented infection and an increase of = 2 SOFA points
consequent to the infection.

Definition of septic shock Sepsis AND an arterial lactate >2 mmol/L AND need for
vasopressor therapy to keep MAP >65 mmHg for > 2 hours despite fluid resuscitation therapy.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Age <18 or > 80 years

- Pregnant

- DNI (do not intubate) orders i.e., Goals of Care other than A

- Patients with a primary admission diagnosis of a traumatic brain injury

- Patients with features of septic shock admitted in the ICU > 24 hours

- Patients with a known history of glucose-6 phosphate dehydrogenase (G-6PD) deficiency

- Patients with a history of renal stones

- Patients with known or suspected scurvy

- Patients previously enrolled in this study

- Plasma sodium >150 mmol/L

- Plasma sodium < 130 mmol/L

- Haemoglobin < 90 g/L

- Jehova's witness

- Receiving isoprenaline

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/12/2023
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Intensive Care Unit Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3050 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Melbourne Health
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Monash Medical Centre
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Florey Institute of Neuroscience and Mental Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Melbourne
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Despite promising observational and phase 1 data, the therapeutic potential of vitamin C for
the management of septic shock has not borne out in recent large multi-centre randomized
controlled trials. There is biological plausibility for benefit with intravenous vitamin C,
and the investigators hypothesize that the doses used in these trials were insufficient to
demonstrate an effect. High-dose vitamin C has been trialed in patients with cancer and burns
and proven to be safe. The investigators have recently demonstrated a dramatic benefit of
high-dose intravenous vitamin C in reversing organ dysfunction in a large mammalian model of
sepsis. The proposed prospective interventional study will be the first to administer
high-dose intravenous vitamin C in critically ill patients with sepsis. The objectives of
this study will be to determine whether high-dose intravenous vitamin C (i) reduces
vasopressor requirement in critically ill patients with septic shock (ii) reverses organ
dysfunction and (iii) is well tolerated.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04796636
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mark P Plummer, PhD
Address 0 0
Melbourne Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Mark P Plummer, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 419708399
Fax 0 0
Email 0 0
mark.plummer@mh.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04796636