Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients

Amsterdam UMC, location VUmc20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Organ Failure Sepsis Systemic Inflammatory Response Syndrome Trauma

Interventions

Ascorbic AcidDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

VU University Medical Center

Amsterdam, Netherlands

Outcomes

Primary Outcomes

Vitamin C plasma concentration

Time frame: Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention

Vitamin C excreted in urine

Time frame: 0-12hours after first intervention; 36-48 hours after first intervention

Secondary Outcomes

Oxalate excretion in urine

Time frame: 0-12hours after first intervention; 36-48 hours after first intervention

F2-isoprostanes (oxidative damage biomarker)

Time frame: 0, 24 and 72 hours after first intervention

CellROX (reactive oxygen species activity in leukocytes)

Time frame: 0 and 24 hours after first intervention

Vasopressor requirements (noradrenalin dose)

Time frame: 0, 12, 24, 48, 72 and 96 hours after first intervention

Renal resistive index (ultrasonography)

Time frame: 0, 4, 24, 72 hours after first intervention

Serum creatinine and creatinine clearance

Time frame: 0, 24, 48, 72, 95 after first intervention

Sequential Organ Failure Assessment (SOFA) score

Time frame: 0, 24, 48, 72, 95 after first intervention

Data from ClinicalTrials.gov

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