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

Amsterdam UMC, location VUmc

Status and phase: Completed; Phase 4

Conditions: Multiple Organ Failure; Trauma; Systemic Inflammatory Response Syndrome; Sepsis

Treatments: Drug: Ascorbic Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT02455180

NL50578.029.14

2014-003680-38 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

20 participants in 4 patient groups

4x 1 gram bolus (q12H) dosage regimen

Experimental group

Description:

1 gram of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 4 grams).

Treatment:

Drug: Ascorbic Acid

4x 5 grams bolus (q12H) dosage regimen

Experimental group

Description:

5 grams of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 20 grams).

Treatment:

Drug: Ascorbic Acid

4 gram continuous dosage regimen

Experimental group

Description:

1 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours

Treatment:

Drug: Ascorbic Acid

20 gram continuous dosage regimen

Experimental group

Description:

5 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours

Treatment:

Drug: Ascorbic Acid