High-dose Intravenous Vitamin C in Patients With Septic Shock

NCT04796636 | Unknown Phase 1 DMC

• 1 other identifier: 2021.026
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis, Severe; Septic Shock

Outcome Measures

Primary Outcomes (1)

• Time to cessation of vasopressor support

  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.

  7 days

Secondary Outcomes (21)

• Plasma C-reactive protein

  24, 48 and 72 hours

• Plasma procalcitonin

  24, 48 and 72 hours

• Plasma thrombomodulin

  24, 48 and 72 hours

• Inflammatory markers

  24, 48 and 72 hours

• Body temperature

  24, 48 and 72 hours

Other Outcomes (2)

• Number of patients that die during their hospital admission

  Through to study completion: 12 months

• Hospital length of stay

  Through to study completion: 12 months

Study Arms (3)

Intermediate dose

EXPERIMENTAL

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

Drug: Sodium Ascorbate

High dose

EXPERIMENTAL

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

Drug: Sodium Ascorbate

Usual care

NO INTERVENTION

Usual care for septic shock. No vitamin C will be given

Interventions

Sodium Ascorbate DRUG

As previously described

High dose; Intermediate dose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Melbourne Health: lead
• Monash Medical Centre: collaborator
• The Florey Institute of Neuroscience and Mental Health: collaborator
• University of Melbourne: collaborator

Study Sites (1)

Intensive Care Unit Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

RECRUITING

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Mark P Plummer, PhD

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark P Plummer, PhD

CONTACT

+61 419708399; mark.plummer@mh.org.au

Adam M Deane, PhD

CONTACT

+61 431967560; adam.deane@mh.org.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label phase 1 randomized controlled trial

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: March 15, 2021
• Study Start: September 27, 2021
• Primary Completion: September 22, 2023
• Study Completion: December 22, 2023
• Last Updated: November 4, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)