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

NCT ID: NCT02455180

Last Updated: 2017-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-11-30

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

4x 1 gram bolus (q12H) dosage regimen

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

Group Type: EXPERIMENTAL

Ascorbic Acid

Intervention Type: DRUG

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.

4x 5 grams bolus (q12H) dosage regimen

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

Group Type: EXPERIMENTAL

Ascorbic Acid

Intervention Type: DRUG

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.

4 gram continuous dosage regimen

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

Group Type: EXPERIMENTAL

Ascorbic Acid

Intervention Type: DRUG

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.

20 gram continuous dosage regimen

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

Group Type: EXPERIMENTAL

Ascorbic Acid

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Vitamin C

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

H.M. Oudemans-van Straaten, MD, PhD

Intensivist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

H.M. Oudemans-van Straaten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

VU University Medical Center

Amsterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 29522710 (View on PubMed)

Other Identifiers

2014-003680-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL50578.029.14

Identifier Type: -

Identifier Source: org_study_id