NCT02455180

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Mar 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2015

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

May 21, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 27, 2015

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2016

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

August 2, 2017

Status Verified

August 1, 2017

Enrollment Period

1.6 years

First QC Date

May 21, 2015

Last Update Submit

August 1, 2017

Conditions

Multiple Organ FailureSepsisSystemic Inflammatory Response SyndromeTrauma

Keywords

Critical Care

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (7)

  • 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

  • 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

  • +2 more secondary outcomes

Study Arms (4)

4x 1 gram bolus (q12H) dosage regimen

EXPERIMENTAL

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

Drug: Ascorbic Acid

4x 5 grams bolus (q12H) dosage regimen

EXPERIMENTAL

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

Drug: Ascorbic Acid

4 gram continuous dosage regimen

EXPERIMENTAL

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

Drug: Ascorbic Acid

20 gram continuous dosage regimen

EXPERIMENTAL

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

Drug: Ascorbic Acid

Interventions

Ascorbic AcidDRUG

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.

Also known as: Vitamin C
20 gram continuous dosage regimen4 gram continuous dosage regimen4x 1 gram bolus (q12H) dosage regimen4x 5 grams bolus (q12H) dosage regimen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (1)

  • 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.

    PMID: 29522710DERIVED

MeSH Terms

Conditions

Multiple Organ FailureSepsisSystemic Inflammatory Response SyndromeWounds and Injuries

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

ShockPathologic ProcessesPathological Conditions, Signs and SymptomsInfectionsInflammation

Intervention Hierarchy (Ancestors)

Sugar AcidsAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydroxy AcidsCarbohydrates

Study Officials

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

    Amsterdam UMC, location VUmc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Intensivist

Study Record Dates

First Submitted

May 21, 2015

First Posted

May 27, 2015

Study Start

March 1, 2015

Primary Completion

October 1, 2016

Study Completion

November 1, 2016

Last Updated

August 2, 2017

Record last verified: 2017-08

Locations

NL(1)