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.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
sepsis of SIRS (systemische inflammatie) met orgaanfalen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints are plasma concentrations and pharmacokinetic parameters
clearance (Cl), volume of distribution (Vd) and elilmination half life (T* ),
the fraction of retained vitamin C in the body and the fraction/amount of
vitamin C excreted in urine.
Secondary outcome
Secondary endpoints are effect and safety parameters: oxidative damage (F2
isoprostanes), leukocyte reactive oxygen species (ROS) activity in blood and
the development of high anion-gap acidosis. Explorative endpoints are clinical
and biochemical markers of circulation, organ function and injury: sublingual
microcirculation, renal resistive index, changes in noradrenalin dose, serum
creatinine and SOFA score, and the bioimpedance markers resistance, reactance
and phase angle.
Background summary
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
Study 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
Intervention
Patients will receive a daily dose of either 2 or 10 gram vitamin C by
intermittent dosing (half of the daily dose b.i.d.) or by continuous infusion
for two days.
Study burden and risks
Three ml blood will be sampled at baseline, T=1, 2, 4, 8 and 12 hours (trough
level for intermittent dosing) after the first vitamin C dose or start of
vitamin C infusion and a urine sample from the first 12 hours urine collection
(T=0 to T=12 hours) will be taken for determination of vitamin C concentration.
Vitamin C samples (trough samples for intermittent dosing) will be taken at
T=24 and T=36 hours. After the last vitamin C dose or end of the infusion,
blood samples will be taken at T=48, T=72 and T=96 hours. Samples for secondary
and explorative endpoints will be taken at baseline and thereafter different
times per parameter. A total of 48 ml blood will be taken during a period of
five days from an arterial line which is routinely present for monitoring. The
patient will not notice the sampling. The sampling will not impose any risk to
the patient. In addition, sublingual measurement of the microcirculation, renal
echography and bioimpedance measurement will be performed.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
>18 years
Sepsis or SIRS (systemic inflammatory response syndrome), after major surgery or trauma
Non-neurological sequential organ failure score (SOFA) >6
Expected length of ICU stay >96 hours
Informed consent initially the legal representative and later by the patient
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 < 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003680-38-NL |
| CCMO | NL50578.029.15 |