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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02455180
• Other study ID #: NL50578.029.14
• Secondary ID: 2014-003680-38
• Status: Completed
• Phase: Phase 4
• First received: May 21, 2015
• Last updated: August 1, 2017
• Start date: March 2015
• Est. completion date: November 2016

Study information

• Verified date: August 2017
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Multiple Organ Failure
• Sepsis
• Systemic Inflammatory Response Syndrome
• Trauma

Intervention

Drug:
• Ascorbic 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.

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vitamin C plasma concentration		Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention
Primary	Vitamin C excreted in urine		0-12hours after first intervention; 36-48 hours after first intervention
Secondary	Oxalate excretion in urine		0-12hours after first intervention; 36-48 hours after first intervention
Secondary	F2-isoprostanes (oxidative damage biomarker)		0, 24 and 72 hours after first intervention
Secondary	CellROX (reactive oxygen species activity in leukocytes)		0 and 24 hours after first intervention
Secondary	Vasopressor requirements (noradrenalin dose)		0, 12, 24, 48, 72 and 96 hours after first intervention
Secondary	Renal resistive index (ultrasonography)		0, 4, 24, 72 hours after first intervention
Secondary	Serum creatinine and creatinine clearance		0, 24, 48, 72, 95 after first intervention
Secondary	Sequential Organ Failure Assessment (SOFA) score		0, 24, 48, 72, 95 after first intervention