Study of the way the body absorbs, distributes and gets rid of two different high doses of vitamin C in patients in the intensive care unit

Conditions: 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.
Therapeutic area: Body processes [G] - Biological Phenomena [G16]

Registration Number: EUCTR2014-003680-38-NL

Lead Sponsor: VU university medical center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

>18 years
Sepsis or SIRS (systemic inflammatory response syndrome), after major surgery or trauma
Non-neurological sequential organ failure score >6
Expected length of ICU stay > 96 hours
Informed consent by patient or legal representative

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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. ;Secondary Objective: Not applicable;Primary end point(s): Plasma concentrations vitamin C<br>Fraction of vitamin C excreted in urine in relation to the administered dose<br>Clearance (Cl) (ml/min)<br>Volume of distribution (Vd) (L)<br>Elimination half life (t½) (hours) <br>;Timepoint(s) of evaluation of this end point: 5 days with blood samples at t<0, t=0, 1, 2, 4, 8, 12, 24, 36, 48, 72 and 96 hours

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Reactive oxygen species (ROS) activity in blood (CellROX)<br>Oxidative damage (F2 isoprostanes)<br>Anion gap metabolic acidosis<br>;Timepoint(s) of evaluation of this end point: 5 days with blood samples at t<0, t=1, 4, 8, 24, 48, 72 and 96