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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04796636
Registration number
NCT04796636
Ethics application status
Date submitted
19/01/2021
Date registered
15/03/2021
Titles & IDs
Public title
High-dose Intravenous Vitamin C in Patients With Septic Shock
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Scientific title
HIGH-dose Intravenous VItamin C in Patients With Septic Shock: HIGH-VIS Trial
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Secondary ID [1]
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2021.026
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Universal Trial Number (UTN)
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Trial acronym
HIGH-VIS
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Sepsis, Severe
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Septic Shock
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Condition category
Condition code
Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Infection
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Studies of infection and infectious agents
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Cardiovascular
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Diseases of the vasculature and circulation including the lymphatic system
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Cardiovascular
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Other cardiovascular diseases
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Time to cessation of vasopressor support
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Assessment method [1]
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Time to cessation of vasopressor support (up to day 14). This will be defined as per the VITAMINS trial, as the patient being alive at discontinuation of all vasopressors for at least 4 hours in the presence of MAP \>65 mmHg for the same 4 hour period as reported in the ICU charts. Use of vasopressor will be defined as any use of noradrenaline, adrenaline, vasopressin, metaraminol, dopamine or phenylephrine. Data on doses will be obtained hourly and the doses summed for each study day. Vasopressor dose will be calculated as the sum of norepinephrine and 'norepinephrine equivalent' doses.
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Timepoint [1]
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7 days
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Secondary outcome [1]
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Plasma C-reactive protein
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Assessment method [1]
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Change in plasma C-reactive protein from baseline
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Timepoint [1]
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24, 48 and 72 hours
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Secondary outcome [2]
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Plasma procalcitonin
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Assessment method [2]
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Change in procalcitonin from baseline
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Timepoint [2]
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24, 48 and 72 hours
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Secondary outcome [3]
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Plasma thrombomodulin
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Assessment method [3]
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Change in thrombodulin from baseline
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Timepoint [3]
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24, 48 and 72 hours
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Secondary outcome [4]
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Inflammatory markers
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Assessment method [4]
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Change in IL-6, IL-10 and TNF-alpha from baseline
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Timepoint [4]
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24, 48 and 72 hours
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Secondary outcome [5]
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Body temperature
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Assessment method [5]
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Change in body temperature from baseline
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Timepoint [5]
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24, 48 and 72 hours
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Secondary outcome [6]
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Sequential Organ Failure Assessment score
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Assessment method [6]
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Change in daily Sequential Organ Failure Assessment (SOFA) score: minimum score 0 and maximum score 24 with higher scores meaning worse outcomes
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Timepoint [6]
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7 days
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Secondary outcome [7]
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Cardiovascular Sequential organ failure assessment score
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Assessment method [7]
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Change in cardiovascular component of sequential organ failure assessment score. Scored from 0 to 4 with 4 indicated a worse outcome.
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Timepoint [7]
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7 days
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Secondary outcome [8]
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Neurological Sequential organ failure assessment score
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Assessment method [8]
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Change in neurological component of sequential organ failure assessment score. Scored from 0 to 4 with 4 indicated a worse outcome.
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Timepoint [8]
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7 days
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Secondary outcome [9]
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Haematological Sequential organ failure assessment score
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Assessment method [9]
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Change in haematological component of sequential organ failure assessment score. Scored from 0 to 4 with 4 indicated a worse outcome.
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Timepoint [9]
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7 days
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Secondary outcome [10]
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Liver Sequential organ failure assessment score
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Assessment method [10]
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Change in liver component of sequential organ failure assessment score. Scored from 0 to 4 with 4 indicated a worse outcome.
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Timepoint [10]
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7 days
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Secondary outcome [11]
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Renal Sequential organ failure assessment score
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Assessment method [11]
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Change in renal component of sequential organ failure assessment score. Scored from 0 to 4 with 4 indicated a worse outcome.
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Timepoint [11]
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7 days
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Secondary outcome [12]
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Respiratory Sequential organ failure assessment score
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Assessment method [12]
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Change in respiratory component of sequential organ failure assessment score. Scored from 0 to 4 with 4 indicated a worse outcome.
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Timepoint [12]
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7 days
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Secondary outcome [13]
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Maximum plasma concentration of vitamin C (cMax)
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Assessment method [13]
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Maximum plasma concentration CMax within 72 hours
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Timepoint [13]
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72 hours
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Secondary outcome [14]
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Area under the vitamin C plasma concentration versus time curve
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Assessment method [14]
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Area under the vitamin C plasma concentration versus time curve
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Timepoint [14]
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72 hours
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Secondary outcome [15]
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Vitamin C plasma elimination half-life
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Assessment method [15]
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Vitamin C plasma elimination half-life
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Timepoint [15]
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72 hours
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Secondary outcome [16]
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Urinary markers of renal injury
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Assessment method [16]
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Change in urinary KIM-1 and NGAL from baseline
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Timepoint [16]
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72 hours
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Secondary outcome [17]
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Plasma cystatin C
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Assessment method [17]
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Change in plasma cystatin C from baseline
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Timepoint [17]
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72 hours
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Secondary outcome [18]
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Plasma proteomics
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Assessment method [18]
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Change in proteomics from baseline
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Timepoint [18]
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72 hours
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Secondary outcome [19]
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Number of patients screened
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Assessment method [19]
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Number of patients screened
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Timepoint [19]
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Duration of study: 12 months
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Secondary outcome [20]
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Randomised to screened patient ratio
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Assessment method [20]
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Ratio of patients randomized to the study compared to the number of patients screened
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Timepoint [20]
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Duration of study: 12 months
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Secondary outcome [21]
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Percentage of randomized patients compliant with study protocol
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Assessment method [21]
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Compliance with vitamin C drug regimens
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Timepoint [21]
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Duration of study: 12 months
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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.
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Minimum age
18
Years
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Maximum age
80
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
27/09/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
22/12/2023
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Actual
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Sample size
Target
30
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Intensive Care Unit Royal Melbourne Hospital - Melbourne
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Recruitment postcode(s) [1]
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3050 - Melbourne
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Funding & Sponsors
Primary sponsor type
Other
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Name
Melbourne Health
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Monash Medical Centre
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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The Florey Institute of Neuroscience and Mental Health
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Address [2]
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Country [2]
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Other collaborator category [3]
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Other
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Name [3]
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University of Melbourne
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Address [3]
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Country [3]
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT04796636
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Mark P Plummer, PhD
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Address
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Melbourne Health
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Mark P Plummer, PhD
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Address
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Country
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Phone
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+61 419708399
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
Individual participant data will not be made available to a third-party.
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04796636