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

Sponsor
Amsterdam UMC, location VUmc (Other)
Overall Status
Completed
CT.gov ID
NCT02455180
Collaborator
(none)
20
Enrollment
1
Location
4
Arms
20.1
Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Ascorbic Acid
 Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients
Study Start Date :
Mar 1, 2015
Actual Primary Completion Date :
Oct 1, 2016
Actual Study Completion Date :
Nov 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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).

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.
Other Names:
  • Vitamin C

    		•
    Experimental: 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).

    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.
    Other Names:
  • Vitamin C

    		•
    Experimental: 4 gram continuous dosage regimen

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

    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.
    Other Names:
  • Vitamin C

    		•
    Experimental: 20 gram continuous dosage regimen

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

    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.
    Other Names:
  • Vitamin C

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Vitamin C plasma concentration [Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention]

    2. Vitamin C excreted in urine [0-12hours after first intervention; 36-48 hours after first intervention]

    Secondary Outcome Measures

    1. Oxalate excretion in urine [0-12hours after first intervention; 36-48 hours after first intervention]

    2. F2-isoprostanes (oxidative damage biomarker) [0, 24 and 72 hours after first intervention]

    3. CellROX (reactive oxygen species activity in leukocytes) [0 and 24 hours after first intervention]

    4. Vasopressor requirements (noradrenalin dose) [0, 12, 24, 48, 72 and 96 hours after first intervention]

    5. Renal resistive index (ultrasonography) [0, 4, 24, 72 hours after first intervention]

    6. Serum creatinine and creatinine clearance [0, 24, 48, 72, 95 after first intervention]

    7. Sequential Organ Failure Assessment (SOFA) score [0, 24, 48, 72, 95 after first intervention]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 VU University Medical Center Amsterdam Netherlands 1081 HV

    Sponsors and Collaborators

    • Amsterdam UMC, location VUmc

    Investigators

    • Principal Investigator: H.M. Oudemans-van Straaten, MD, PhD, Amsterdam UMC, location VUmc

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    H.M. Oudemans-van Straaten, MD, PhD, Intensivist, Amsterdam UMC, location VUmc
    ClinicalTrials.gov Identifier:
    NCT02455180
    Other Study ID Numbers:
    • NL50578.029.14
    • 2014-003680-38
    First Posted:
    May 27, 2015
    Last Update Posted:
    Aug 2, 2017
    Last Verified:
    Aug 1, 2017
    Keywords provided by H.M. Oudemans-van Straaten, MD, PhD, Intensivist, Amsterdam UMC, location VUmc
    Critical Care
    Additional relevant MeSH terms:
    Systemic Inflammatory Response Syndrome
    Multiple Organ Failure
    Ascorbic Acid

    Study Results

    No Results Posted as of Aug 2, 2017