Multiple Organ Failure, Sepsis, Systemic Inflammatory Response Syndrome, Trauma
Conditions
Keywords
Critical Care
Brief summary
The purpose of this study is to determine the pharmacokinetic properties of two different dosage regimens of intravenous vitamin C in patients admitted to the Intensive Care Unit with life-threatening illness.
Detailed description
Rationale: Critically ill patients with trauma or sepsis exhibit a high degree of vitamin C deficiency at ICU admission and vitamin C plasma concentrations decrease even more during the first three days of admission. Vitamin C is a natural anti-oxidant and crucial for endothelial and organ protection Objective: To determine the pharmacokinetics of two high dose regimens of intravenous vitamin C in critically ill patients, in particular the attained plasma concentration and the fraction retained in the body and excreted in urine. Study design: Prospective randomized controlled pharmacokinetic intervention study Study population: Adult critically ill patients admitted to the ICU of the VU University Medical Center, Amsterdam, with sepsis or SIRS after major surgery or trauma with a non-neurological sequential organ failure (SOFA) score \>6 and an expected length of ICU stay of \>96 hours. Intervention (if applicable): Patients will receive either 2 or 10 gram/day vitamin C intravenously twice daily for two days in bolus or continuous infusion.
Interventions
DRUGAscorbic Acid
Patients receive vitamin C 4 times in either high (5g) or moderate (1g) dose. Vitamin C will be administered intravenously (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands) in 50ml of NaCl 0.9%, infused over 30 minutes.
Sponsors
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sepsis or Systemic Inflammatory Response Syndrome (SIRS) after major surgery or trauma; * Non-neurological sequential organ failure assessment (SOFA) score \>6; * Expected length of ICU stay \> 96 hours; * Written proxy consent by legal representative.
Exclusion criteria
* Admission after out of hospital cardiac arrest * Prior use of supplemental vitamin C in the week before * Major bleeding * Pre-existent renal insufficiency defined as an eGFR of \< 30 ml/min/1.73 m2 (stadium 4-5) * Expected need for renal replacement therapy within 48 hours * Known glucose 6-phosphate dehydrogenase deficiency * History of urolithiasis or oxalate nephropathy * Previous use of prolonged high dose vitamin C supplements * Hemochromatosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Vitamin C plasma concentration | Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention |
| Vitamin C excreted in urine | 0-12hours after first intervention; 36-48 hours after first intervention |
Secondary
| Measure | Time frame |
|---|---|
| CellROX (reactive oxygen species activity in leukocytes) | 0 and 24 hours after first intervention |
| Vasopressor requirements (noradrenalin dose) | 0, 12, 24, 48, 72 and 96 hours after first intervention |
| Oxalate excretion in urine | 0-12hours after first intervention; 36-48 hours after first intervention |
| Serum creatinine and creatinine clearance | 0, 24, 48, 72, 95 after first intervention |
| Sequential Organ Failure Assessment (SOFA) score | 0, 24, 48, 72, 95 after first intervention |
| Renal resistive index (ultrasonography) | 0, 4, 24, 72 hours after first intervention |
| F2-isoprostanes (oxidative damage biomarker) | 0, 24 and 72 hours after first intervention |
Countries
Netherlands
Outcome results
None listed