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The Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock Trial (VITAMINS)

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ClinicalTrials.gov Identifier: NCT03333278
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : October 10, 2019
Sponsor:
Collaborators:
Austin Hospital, Melbourne Australia
Melbourne Health
Barwon Health
Monash Health
The Alfred
Wellington Hospital
Western Health, Australia
Information provided by (Responsible Party):
anzicrc, Australian and New Zealand Intensive Care Research Centre

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.


Condition or disease Intervention/treatment Phase
Shock, Septic Critically Ill Vasoplegic Syndrome Sepsis Drug: Vitamin C Drug: Thiamine Drug: Hydrocortisone, Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-centre, Randomised, Open-label controlled Trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : May 2, 2018
Actual Primary Completion Date : July 16, 2019
Actual Study Completion Date : October 6, 2019


Arm Intervention/treatment
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)
Drug: Vitamin C
Ascorbic acid 1.5g every 6 hours i.v. while in ICU, until shock resolution for a maximum of ten days
Other Name: Ascorbic acid

Drug: Thiamine
Thiamine 200mg every 12 hours i.v. while in ICU, until shock resolution for a maximum of ten days
Other Name: Vitamin B1

Drug: 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.
Other Name: Solu Cortef

Control
Hydrocortisone (50mg every 6 hours)
Drug: 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.
Other Name: Solu Cortef




Primary Outcome Measures :
  1. Time alive and free of vasopressors at day 7 (168 hours) after randomization. [ Time Frame: 7 days (168 hours) ]
    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.


Secondary Outcome Measures :
  1. ICU mortality [ Time Frame: 90 days after randomization ]
    Patient died during the ICU admission

  2. Alive and ICU-free days at day 28 calculated as the number of days alive and out of the ICU to day 28 [ Time Frame: 28 days after randomization ]
    Alive and ICU-free days calculated as the number of days alive and out of the ICU to day 28

  3. Hospital mortality [ Time Frame: 90 days after randomization ]
    Patient died during the hospital admission

  4. 28-day mortality [ Time Frame: 28 days after randomization ]
    Patient died within 28 days after randomization

  5. 90-day mortality [ Time Frame: 90 days after randomization ]
    Patient died within 90 days after randomization

  6. Delta of Sequential Organ Failure Assessment (SOFA) score at 72 hours [ Time Frame: 72 hours after randomization ]

    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.


  7. Hospital length of stay [ Time Frame: 90 days after randomization ]
    Duration the patient stayed in the hospital

  8. 28 day cumulative vasopressor free hours [ Time Frame: 28 days after randomization ]
    Cumulative vasopressor free hours from shock resolution to day28 post randomisation

  9. 28 day cumulative invasive mechanical ventilation free hours [ Time Frame: 28 days after randomization ]
    Cumulative invasive mechanical ventilation-free hours during the 28 day period post randomisation

  10. RRT duration [ Time Frame: 28 days after randomization ]
    Length of renal replacement therapy dependency during the 28 day period post randomisation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03333278


Locations
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Australia, Victoria
Monash Health (Monash Medical Centre and Dandenong Hospital)
Clayton, Victoria, Australia, 3468
Geelong University Hospital
Geelong, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia, 3084
Alfred Hospital
Melbourne, Victoria, Australia, 3004
Western Health (Footscray & Sunshine Hospital)
Melbourne, Victoria, Australia, 3021
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Brazil
Cancer Institute of the State of São Paulo
São Paulo, Brazil, 01246-000
New Zealand
Wellington Hospital
Wellington, New Zealand
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
Austin Hospital, Melbourne Australia
Melbourne Health
Barwon Health
Monash Health
The Alfred
Wellington Hospital
Western Health, Australia
Investigators
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Principal Investigator: Rinaldo Bellomo, Professor Austin Hospital, Melbourne Australia
Principal Investigator: Nora Luethi, MD ANZIC-RC
Principal Investigator: Tomoko Fujii, MD ANZIC-RC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: anzicrc, Professor Rinaldo Bellomo, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT03333278     History of Changes
Other Study ID Numbers: HREC17Austin238
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data Sharing Policy is available from the website.
URL: https://www.monash.edu/__data/assets/pdf_file/0010/1790875/terms_of_ref.pdf

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by anzicrc, Australian and New Zealand Intensive Care Research Centre:
Critical Care
Shock, Septic
Ascorbic Acid
Adult
Additional relevant MeSH terms:
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Shock, Septic
Vasoplegia
Shock
Critical Illness
Pathologic Processes
Disease Attributes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Vitamins
Ascorbic Acid
Thiamine
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anti-Inflammatory Agents
Vitamin B Complex