Sepsis
Conditions
Interventions
Trade Name: LAROSCORBINE
Product Name: Ascorbic acid
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for infusi
Sponsors
Université de Sherbrooke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In both countries: 1) Patients = 18 years old; 2) Admitted to the ICU with proven or suspected infection as the main diagnosis; 3) Currently treated with a continuous intravenous infusion of vasopressors (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine); In France: 5) Patient (or his representant) who has signed an informed and written consent; 6) Affiliation to a social security system or to an universal health coverage (Couverture Maladie Universelle, CMU); 7) Patients under guardianship or curatorship will be included; 8) Patients in case of simple emergency (legal definition) will be included. 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 700 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1) > 24 hours of ICU admission; 2) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency; 3) Pregnancy; 4) Known allergy to vitamin C; or to one of the excipients in particular methyl parahydroxybenzoate (E218) or propyl (E216); 5) Known kidney stones within the past 1 year; 6) Received any intravenous vitamin C during this hospitalization unless incorporated in parenteral nutrition; 7) Expected death or withdrawal of life-sustaining treatments within 48 hours; 8) Previously enrolled in this study; 9) Previously enrolled in a trial for which co-enrolment is not allowed (co-enrolment to be determined case by case).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: both assessed at 28 days.;Primary end point(s): The primary outcome will be a composite of death or persistent organ dysfunction (defined as dependency on mechanical ventilation, renal replacement, or vasopressors) ;Main Objective: To compare the effect of high-dose intravenous vitamin C vs. placebo on a composite of death or persistent organ dysfunction – defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors – assessed at 28 days on intensive care unit (ICU) patients.; Secondary Objective: To compare the effect of high-dose intravenous vitamin C vs. placebo on: 1)6-month mortality 2)6-month HRQoL 3)organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU) 4)global tissue dysoxia 5)occurrence of stage 3 acute kidney injury (KDIGO criteria) 6)Acute hemolysis as defined by: -clinician judgment of hemolysis, as recorded in the chart, OR -hemoglobin drop of at least 25 g/L within 24 hours of a dose of IMP + 2 of the following: ?reticulocyte count >2 times upper limit of normal at clinical site lab ?haptoglobin 2 times upper limit of normal at clinical site lab ?Lactate dehydrogenase (LDH) >2 times upper limit of normal at clinical site lab Severe hemolysis: -hemoglobin < 75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells 7)hypoglycemia as defined as core lab-validated glucose level < 3.8 mmol/L •To assess baseline vitamin C levels | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Up to day 28.; Secondary end point(s): The secondary outcomes will include: 1) Persistent organ dysfunction-free days in ICU, up to day 28. 2) Mortality at 6 months. 3) HRQoL in 6-month survivors assessed by the EuroQol-5D (EQ-5D). This questionnaire is a standardised measure of health status developed to provide a simple, generic measure of health for clinical and economic appraisal. It is made up for two components; health state description and evaluation. The health status is measured in terms of five dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In evaluation part, the respondents evaluate their overall health status using the visual analogue scale. See Figure 4. 4) Global tissue dysoxia assessed by serum lactate concentration.24 This will be assessed using liquid chromatography technique coupled with tandem mass spectrometry (LC-MS/MS). 5) Organ function (including renal function) assessed by the SOFA score (Table 1) (days 1, 2, 3, 4, 7, 10, 14, and 28); 6) Occurrence of stage 3 acute kidney injury as defined by KDIGO criteria18 daily; 7) Acute hemolysis as diagnosed by the clinical site team (daily); 8) Hypoglycemia | — |
Countries
Canada, France, India, New Zealand, Saudi Arabia
Contacts
Public Contactisabelle vivaldo
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
Outcome results
None listed