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

Phase 4

Completed

• Conditions: Multiple Organ Failure; Sepsis; Systemic Inflammatory Response Syndrome; Trauma
• Interventions: Drug: Ascorbic Acid

• Registration Number: NCT02455180
• Lead Sponsor: Amsterdam UMC, location VUmc

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.

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-05-21
• Study First Submitted QC: 2015-05-21
• Study First Posted: 2015-05-27
• Primary Completion: 2016-10
• Study Completion: 2016-11
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-01
• Last Update Posted: 2017-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4x 5 grams bolus (q12H) dosage regimen	Ascorbic Acid	5 grams of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 20 grams).
4x 1 gram bolus (q12H) dosage regimen	Ascorbic Acid	1 gram of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 4 grams).
4 gram continuous dosage regimen	Ascorbic Acid	1 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours
20 gram continuous dosage regimen	Ascorbic Acid	5 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Renal resistive index (ultrasonography)	0, 4, 24, 72 hours after first intervention
Oxalate excretion in urine	0-12hours after first intervention; 36-48 hours after first intervention
F2-isoprostanes (oxidative damage biomarker)	0, 24 and 72 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

Trial Locations

Locations (1)

VU University Medical Center; 🇳🇱 Amsterdam, Netherlands