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

• Status: Completed
• Trial end date: 2019-10-06
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Australian and New Zealand Intensive Care Research Centre
• Collaborators: Austin Hospital, Melbourne Australia; Barwon Health; Melbourne Health; Monash Health; Monash Medical Centre; St Vincent's Hospital Melbourne; The Alfred; Wellington Hospital; Western Health, Australia
• Treatments: Ascorbic Acid; Cortisol succinate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Thiamine; Vitamins

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