Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
MY TRIALS
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Register a trial
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
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/study/NCT03333278
Registration number
NCT03333278
Ethics application status
Date submitted
29/10/2017
Date registered
6/11/2017
Titles & IDs
Public title
The Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock Trial
Query!
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
Query!
Secondary ID [1]
0
0
HREC17Austin238
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
VITAMINS
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Shock, Septic
0
0
Query!
Critically Ill
0
0
Query!
Vasoplegic Syndrome
0
0
Query!
Sepsis
0
0
Query!
Condition category
Condition code
Inflammatory and Immune System
0
0
0
0
Query!
Other inflammatory or immune system disorders
Query!
Cardiovascular
0
0
0
0
Query!
Diseases of the vasculature and circulation including the lymphatic system
Query!
Cardiovascular
0
0
0
0
Query!
Other cardiovascular diseases
Query!
Intervention/exposure
Study type
Interventional
Query!
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Time alive and free of vasopressors at day 7 (168 hours) after randomization.
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
7 days (168 hours)
Query!
Secondary outcome [1]
0
0
ICU mortality
Query!
Assessment method [1]
0
0
Patient died during the ICU admission
Query!
Timepoint [1]
0
0
90 days after randomization
Query!
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
Query!
Assessment method [2]
0
0
Alive and ICU-free days calculated as the number of days alive and out of the ICU to day 28
Query!
Timepoint [2]
0
0
28 days after randomization
Query!
Secondary outcome [3]
0
0
Hospital mortality
Query!
Assessment method [3]
0
0
Patient died during the hospital admission
Query!
Timepoint [3]
0
0
90 days after randomization
Query!
Secondary outcome [4]
0
0
28-day mortality
Query!
Assessment method [4]
0
0
Patient died within 28 days after randomization
Query!
Timepoint [4]
0
0
28 days after randomization
Query!
Secondary outcome [5]
0
0
90-day mortality
Query!
Assessment method [5]
0
0
Patient died within 90 days after randomization
Query!
Timepoint [5]
0
0
90 days after randomization
Query!
Secondary outcome [6]
0
0
Delta of Sequential Organ Failure Assessment (SOFA) score at 72 hours
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
72 hours after randomization
Query!
Secondary outcome [7]
0
0
Hospital length of stay
Query!
Assessment method [7]
0
0
Duration the patient stayed in the hospital
Query!
Timepoint [7]
0
0
90 days after randomization
Query!
Secondary outcome [8]
0
0
28 day cumulative vasopressor free hours
Query!
Assessment method [8]
0
0
Cumulative vasopressor free hours from shock resolution to day28 post randomisation
Query!
Timepoint [8]
0
0
28 days after randomization
Query!
Secondary outcome [9]
0
0
28 day cumulative invasive mechanical ventilation free hours
Query!
Assessment method [9]
0
0
Cumulative invasive mechanical ventilation-free hours during the 28 day period post randomisation
Query!
Timepoint [9]
0
0
28 days after randomization
Query!
Secondary outcome [10]
0
0
RRT duration
Query!
Assessment method [10]
0
0
Length of renal replacement therapy dependency during the 28 day period post randomisation
Query!
Timepoint [10]
0
0
28 days after randomization
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
2/05/2018
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
6/10/2019
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
216
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Monash Health (Monash Medical Centre and Dandenong Hospital) - Clayton
Query!
Recruitment hospital [2]
0
0
Geelong University Hospital - Geelong
Query!
Recruitment hospital [3]
0
0
Austin Health - Heidelberg
Query!
Recruitment hospital [4]
0
0
Alfred Hospital - Melbourne
Query!
Recruitment hospital [5]
0
0
Western Health (Footscray & Sunshine Hospital) - Melbourne
Query!
Recruitment hospital [6]
0
0
Royal Melbourne Hospital - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
3468 - Clayton
Query!
Recruitment postcode(s) [2]
0
0
- Geelong
Query!
Recruitment postcode(s) [3]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [4]
0
0
3004 - Melbourne
Query!
Recruitment postcode(s) [5]
0
0
3021 - Melbourne
Query!
Recruitment postcode(s) [6]
0
0
3050 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
Brazil
Query!
State/province [1]
0
0
São Paulo
Query!
Country [2]
0
0
New Zealand
Query!
State/province [2]
0
0
Wellington
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
Australian and New Zealand Intensive Care Research Centre
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Other
Query!
Name [1]
0
0
Austin Hospital, Melbourne Australia
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Other collaborator category [2]
0
0
Other
Query!
Name [2]
0
0
Melbourne Health
Query!
Address [2]
0
0
Query!
Country [2]
0
0
Query!
Other collaborator category [3]
0
0
Government body
Query!
Name [3]
0
0
Barwon Health
Query!
Address [3]
0
0
Query!
Country [3]
0
0
Query!
Other collaborator category [4]
0
0
Other
Query!
Name [4]
0
0
Monash Health
Query!
Address [4]
0
0
Query!
Country [4]
0
0
Query!
Other collaborator category [5]
0
0
Other
Query!
Name [5]
0
0
The Alfred
Query!
Address [5]
0
0
Query!
Country [5]
0
0
Query!
Other collaborator category [6]
0
0
Government body
Query!
Name [6]
0
0
Wellington Hospital
Query!
Address [6]
0
0
Query!
Country [6]
0
0
Query!
Other collaborator category [7]
0
0
Government body
Query!
Name [7]
0
0
Western Health, Australia
Query!
Address [7]
0
0
Query!
Country [7]
0
0
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/study/NCT03333278
Query!
Trial related presentations / publications
Fujii T, Luethi N, Young PJ, Frei DR, Eastwood GM, French CJ, Deane AM, Shehabi Y, Hajjar LA, Oliveira G, Udy AA, Orford N, Edney SJ, Hunt AL, Judd HL, Bitker L, Cioccari L, Naorungroj T, Yanase F, Bates S, McGain F, Hudson EP, Al-Bassam W, Dwivedi DB, Peppin C, McCracken P, Orosz J, Bailey M, Bellomo R; VITAMINS Trial Investigators. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA. 2020 Feb 4;323(5):423-431. doi: 10.1001/jama.2019.22176. Fujii T, Udy AA, Deane AM, Luethi N, Bailey M, Eastwood GM, Frei D, French C, Orford N, Shehabi Y, Young PJ, Bellomo R; VITAMINS trial investigators. Vitamin C, Hydrocortisone and Thiamine in Patients with Septic Shock (VITAMINS) trial: study protocol and statistical analysis plan. Crit Care Resusc. 2019 Jun;21(2):119-125.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Rinaldo Bellomo, Professor
Query!
Address
0
0
Austin Hospital, Melbourne Australia
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
Query!
What data in particular will be shared?
Data Sharing Policy is available from the website.
Query!
When will data be available (start and end dates)?
Query!
Available to whom?
Query!
Available for what types of analyses?
Query!
How or where can data be obtained?
IPD available at link: https://www.monash.edu/__data/assets/pdf_file/0010/1790875/terms_of_ref.pdf
Query!
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/NCT03333278