None listed
Conditions
Brief summary
Our group has recently undertaken studies of mega-dose intravenous sodium ascorbate in septic sheep (up to 3.75 g/kg) and demonstrated a dramatic reversal of organ dysfunction. We have recently completed a pilot study administering sodium ascorbate to critically ill patients with sepsis at a single dose of 60 grams over 6 hours. Sodium ascorbate was well tolerated, increased urine output, and decreased the requirement for medication to support the blood pressure (vasopressors). The study will determine whether mega-dose sodium ascorbate at a dose of 180 grams can decrease the time to weaning from blood pressure support for patients with sepsis and whether it improves other markers of organ dysfunction. If there is a signal for benefit, this trial will establish feasibility for a subsequent larger definitive study.
Interventions
9% sodium ascorbate will be presented in 5% dextrose and administered intravenously through a dedicated lumen of a central or peripheral line as a 45 gram loading dose over one hour (500 mL) followed by a continuous infusion of 135 grams over 17 hours (88 ml/hr). This will be prepared by a clinical trials or registered nurse and prescribed by the treating medical team.
A plasma or blood sodium level > 150 mmol/L at any time during the intervention period will trigger an immediate reduction in t
9% sodium ascorbate will be presented in 5% dextrose and administered intravenously through a dedicated lumen of a central or peripheral line as a 45 gram loading dose over one hour (500 mL) followed by a continuous infusion of 135 grams over 17 hours (88 ml/hr). This will be prepared by a clinical trials or registered nurse and prescribed by the treating medical team. A plasma or blood sodium level > 150 mmol/L at any time during the intervention period will trigger an immediate reduction in the infusion rate by 1/3 from 88 mL/hr to 59 mL/hr. The infusion rate will be reduced once only and remain at the reduced level until the full dose is administered or until the sodium reaches permanent stopping criteria (> 155 mmol/L).
Sponsors
The Florey Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
• Age 18 – 80 years • Diagnosis of septic shock: Suspected or proven infection AND an arterial lactate >2 mmol/L at any time in the preceding 24 hours AND need for vasopressor therapy at a noradrenaline equivalent dose greater than or equal to 5 µg/min to keep mean arterial pressure greater than or equal to 65 mmHg despite fluid resuscitation therapy at the time of randomisation.
Exclusion criteria
• Age 80 years • Pregnancy confirmed on either urine or blood sample • Creatinine > 150 mmol/L • Type 1 diabetes mellitus • History of ketoacidosis • Congestive heart failure • Use of SGLT2 Inhibitors • Renal replacement therapy • DNI (do not intubate) orders • Patients with a known history of glucose-6 phosphate dehydrogenase (G-6PD) deficiency • G6PD positivity on BinaxNOWTM G6PD Point-of-Care Qualtitative Rapid Diagnostic Test (Lake Forest, Illinois, USA) • Patients with a history of renal stones or oxaluria • Patients with known or suspected scurvy • Patients previously enrolled in this study • Plasma sodium > 140 mmol/L • Plasma sodium < 125 mmol/L • Haemoglobin < 80 g/L • People for whom preservation of red blood cells is of high clinical priority, e.g Jehova’s Witnesses • Receiving isoprenaline • Anticipated to require intravenous sodium bicarbonate during the intervention period • Persons who have shown hypersensitivity to any of the components of sodium ascorbate
Outcome results
None listed