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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03333278




Registration number
NCT03333278
Ethics application status
Date submitted
29/10/2017
Date registered
6/11/2017
Date last updated
10/10/2019

Titles & IDs
Public title
The Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock Trial
Scientific title
The VitamIn C, HydrocorTisone and ThiAMINe in Patients With Septic Shock Trial (VITAMINS Trial) - A Prospective, Feasibility, Pilot, Multi-centre, Randomised, Open-label Controlled Trial
Secondary ID [1] 0 0
HREC17Austin238
Universal Trial Number (UTN)
Trial acronym
VITAMINS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Shock, Septic 0 0
Critically Ill 0 0
Vasoplegic Syndrome 0 0
Sepsis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
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 - Vitamin C
Treatment: Drugs - Thiamine
Treatment: Drugs - Hydrocortisone,

Active Comparator: Vitamins - intravenous: Ascorbic acid (Vitamin C: 1.5g every 6 hours) Thiamine (Vitamin B1: 200mg every 12 hours) Hydrocortisone (50mg every 6 hours)

Other: Control - Hydrocortisone (50mg every 6 hours)


Treatment: Drugs: Vitamin C
Ascorbic acid 1.5g every 6 hours i.v. while in ICU, until shock resolution for a maximum of ten days

Treatment: Drugs: Thiamine
Thiamine 200mg every 12 hours i.v. while in ICU, until shock resolution for a maximum of ten days

Treatment: Drugs: Hydrocortisone,
Hydrocortisone 50mg every 6 hours i.v while in ICU, until shock resolution or for a maximum of 7 days, then tapered or stopped.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time alive and free of vasopressors at day 7 (168 hours) after randomization. - This is defined by the patient being alive at discontinuation of all vasopressors for at least 4 hours in the presence of a MAP>65 mmHg for the same 4 hour period as recorded in the ICU charts and censored at 7 days. If a patient dies while on vasopressor therapy, in such a patient, the time alive and vasopressor free time will be 0 - This approach will correct for the competing effect of mortality on duration of vasopressor therapy.
Timepoint [1] 0 0
7 days (168 hours)
Secondary outcome [1] 0 0
ICU mortality - Patient died during the ICU admission
Timepoint [1] 0 0
90 days after randomization
Secondary outcome [2] 0 0
Alive and ICU-free days at day 28 calculated as the number of days alive and out of the ICU to day 28 - Alive and ICU-free days calculated as the number of days alive and out of the ICU to day 28
Timepoint [2] 0 0
28 days after randomization
Secondary outcome [3] 0 0
Hospital mortality - Patient died during the hospital admission
Timepoint [3] 0 0
90 days after randomization
Secondary outcome [4] 0 0
28-day mortality - Patient died within 28 days after randomization
Timepoint [4] 0 0
28 days after randomization
Secondary outcome [5] 0 0
90-day mortality - Patient died within 90 days after randomization
Timepoint [5] 0 0
90 days after randomization
Secondary outcome [6] 0 0
Delta of Sequential Organ Failure Assessment (SOFA) score at 72 hours - defined as the initial total SOFA* score minus the day three (72 hours) SOFA score
*total SOFA = Sequential Organ Failure Assessment = sum of each organ system point score. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The organ scores are ranging from 0-4, with the best score being 0 and the worst being 4 points. The maximal (and worst) total SOFA score is 24 points.
Timepoint [6] 0 0
72 hours after randomization
Secondary outcome [7] 0 0
Hospital length of stay - Duration the patient stayed in the hospital
Timepoint [7] 0 0
90 days after randomization
Secondary outcome [8] 0 0
28 day cumulative vasopressor free hours - Cumulative vasopressor free hours from shock resolution to day28 post randomisation
Timepoint [8] 0 0
28 days after randomization
Secondary outcome [9] 0 0
28 day cumulative invasive mechanical ventilation free hours - Cumulative invasive mechanical ventilation-free hours during the 28 day period post randomisation
Timepoint [9] 0 0
28 days after randomization
Secondary outcome [10] 0 0
RRT duration - Length of renal replacement therapy dependency during the 28 day period post randomisation
Timepoint [10] 0 0
28 days after randomization

Eligibility
Key inclusion criteria
Patient in the intensive care unit (ICU) with septic shock:

- Blood lactate >2 mmol/L, despite adequate fluid resuscitation AND

- need for continuous vasopressor therapy to keep mean arterial pressure (MAP) >65 mmHg
for >2 hours
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age < 18 years

2. Pregnancy

3. DNR (do not resuscitate)/DNI (do not intubate) orders

4. Death is deemed to be imminent or inevitable during this admission, and either the
attending physician, patient or substitute decision-maker is not committed to active
treatment

5. Patients with known HIV infection

6. Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency

7. Patients transferred from another ICU or hospital with a diagnosis of a septic shock
for > 24 hours

8. Patients with a diagnosis of a septic shock for > 24 hours

9. Patients with known or suspected

- a. history of oxalate nephropathy or hyperoxaluria

- b. short bowel syndrome or severe fat-malabsorption

- c. acute beri-beri disease

- d. acute Wernicke's encephalopathy

- e. malaria

- f. scurvy

- g. Addison's disease

- h. Cushing's disease

10. Clinician expects to prescribe systemic glucocorticoids for an indication other than
septic shock (not including nebulised or inhaled corticosteroid)

11. Patient is receiving treatment for systemic fungal infection or has documented
Strongyloides infection at the time of randomisation

12. Patient with known chronic iron overload due to iron storage and other diseases

13. Patient previously enrolled in this study

14. Clinician expects to prescribe high dose vitamin C for another indication

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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] 0 0
Monash Health (Monash Medical Centre and Dandenong Hospital) - Clayton
Recruitment hospital [2] 0 0
Geelong University Hospital - Geelong
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Western Health (Footscray & Sunshine Hospital) - Melbourne
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3468 - Clayton
Recruitment postcode(s) [2] 0 0
- Geelong
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3021 - Melbourne
Recruitment postcode(s) [6] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
São Paulo
Country [2] 0 0
New Zealand
State/province [2] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
Australian and New Zealand Intensive Care Research Centre
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Austin Hospital, Melbourne Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Melbourne Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Barwon Health
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Monash Health
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
The Alfred
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Wellington Hospital
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Western Health, Australia
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Sepsis has been characterised as a dysregulated host response to infection. Adjunctive
therapies targeting the inflammatory cascade are being increasingly explored, although to
date, have failed to demonstrate consistent benefit, and sepsis continues to manifest poor
outcomes. Hospital mortality in patients with septic shock remains as high as 22% in
Australia and New Zealand. From a global perspective, 31 million sepsis and 19 million severe
sepsis cases are expected to be treated in hospitals all over the world per year.

To date, experimental data have reported that both high dose intravenous vitamin C and
corticosteroids attenuate the acceleration of the inflammatory cascade and possibly reduce
the endothelial injury characteristic of sepsis, enhance the release of endogenous
catecholamines and improve vasopressor responsiveness.

Therefore, the investigators plan to conduct a feasibility pilot prospective, multi-centre,
randomised, open-label, trial in ICU patients with septic shock to test whether the
intravenous administration of high dose Vitamin C (6g/d), Thiamine (400mg/d) and
Hydrocortisone (200mg/d) leads to a more rapid resolution shock and vasopressor dependence.
Trial website
https://clinicaltrials.gov/show/NCT03333278
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rinaldo Bellomo, Professor
Address 0 0
Austin Hospital, Melbourne Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications