Clinical trial NCT02455180: Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients
Official title: Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Organ Failure
Sepsis
Systemic Inflammatory Response Syndrome
Trauma
Keywords: Critical Care
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2015-05-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Vitamin C plasma concentration
timeFrame: Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention
measure: Vitamin C excreted in urine
timeFrame: 0-12hours after first intervention; 36-48 hours after first intervention
Secondary outcomes:
measure: Oxalate excretion in urine
timeFrame: 0-12hours after first intervention; 36-48 hours after first intervention
measure: F2-isoprostanes (oxidative damage biomarker)
timeFrame: 0, 24 and 72 hours after first intervention
measure: CellROX (reactive oxygen species activity in leukocytes)
timeFrame: 0 and 24 hours after first intervention
measure: Vasopressor requirements (noradrenalin dose)
timeFrame: 0, 12, 24, 48, 72 and 96 hours after first intervention
measure: Renal resistive index (ultrasonography)
timeFrame: 0, 4, 24, 72 hours after first intervention
measure: Serum creatinine and creatinine clearance
timeFrame: 0, 24, 48, 72, 95 after first intervention
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: 0, 24, 48, 72, 95 after first intervention
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: H.M. Oudemans-van Straaten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Grooth HJ, Manubulu-Choo WP, Zandvliet AS, Spoelstra-de Man AME, Girbes AR, Swart EL, Oudemans-van Straaten HM. Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens. Chest. 2018 Jun;153(6):1368-1377. doi: 10.1016/j.chest.2018.02.025. Epub 2018 Mar 6.