Cardiac Arrest
Conditions
Brief summary
Among patients admitted after an out-of-hospital cardiac arrest (OHCA) in intensive care unit (ICU), almost two thirds of patients will develop in the first hours a post-cardiac arrest (CA) shock. This post-CA shock, combines cardiac and hemodynamic failure, generally resulting in multi-organ failure and early death in up to 35% of patients. Experimental data suggest that intravenous ascorbic acid (vitamin C) may attenuate inflammation and vascular injury related to sepsis or surgery. Preclinical and clinical studies also provide safety data of high dose intravenous vitamin C (\> 200mg/kg/day) with no significant adverse event reported and favorable impact on outcome. Experimental data also suggest beneficial effect of vitamin C in post-CA management with improvement of shock and multi-organ failure with potential benefit on neuroprotection and outcome. The study is a phase II multicenter prospective controlled open-label trial randomized in two parallel groups : * Expérimental group: Standard of care care for post-CA shock + Vitamin C (Vit-C) 200mg/kg/d IV (started as early as possible, no later than 1 h after randomization + thiamin (Vit B1) 200mg every 12 h during 3 days. * Control group: Standard of care care for post CA shock according international guidelines. Patient number to be enrolled : 234, Study duration :24 months and 28 days, Inclusion duration : 24 months, Patient participation : duration : 28 days
Interventions
DRUGVitamin C (Laroscorbine) + Vitamin B1 (Bevitine)
in addition of standard post-CA as the control group, patients will receive an IV high-dose vit-C 50mg/kg infusion every 6 hours, started within the hour after randomization, for 3 days. In addition, all patients will receive intravenous thiamine 200 mg twice a day for 3 days to limit the oxalate production.
DRUGstandard treatment
no intervention Standard IV vit-C supplementation will be allowed for dosages up to 1000 mg a day from day 4 after randomization, as well as thiamin supplementation.
Sponsors
Centre Hospitalier de Bethune
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
University Hospital, Lille
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is a phase II multicenter prospective controlled open-label trial randomized in two parallel groups : * Expérimental group * Control group Patient number to be enrolled : 234, Study duration :24 months and 28 days, Inclusion duration : 24 months, Patient participation : duration : 28 days
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients still comatose (Glasgow coma scale \< 8) after an OHCA of presumed cardiac origin with ROSC \< 60 min; * and treated with a norepinephrin or an epinephrin continuous infusion during at least 30 min before randomization to maintain mean arterial pressure (MAP) ≥ 65 mmHg.
Exclusion criteria
* patients still comatose (Glasgow coma scale \< 8) after an OHCA of presumed cardiac origin with ROSC \< 60 min; * and treated with a norepinephrin or an epinephrin continuous infusion ≥ 0.2µg/kg/h, within 4 hours after OHCA, during at least 30 min/h to maintain mean arterial pressure (MAP) ≥ 65 mmHg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of weaning from vasopressors at day 3 after OHCA. | day 3 | Cumulative incidence of weaning from vasopressors at day 3 after OHCA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of death by refractory shock within 7 days after OHCA. | day 7 after OHCA | Cumulative incidence of death by refractory shock within 7 days after OHCA. |
| the neurological outcome at day 28 after OHCA, with mRS range from 0 to 3. | day 28 after OHCA | Assessed using the mRS (favorable neurological outcome will be considered if mRS range from 0 to 3; Unfavorable neurological outcome will be considered if mRS range from 4 to 6). |
| The maximal vasopressors infusion dose within 3 days after OHCA. | 72 hours after OHCA | The maximal vasopressors infusion dose within 3 days after OHCA. |
| The delta SOFA (sepsis-related organ failure assessment score) is defined as the difference between SOFA admission and SOFA at 72 hours after OHCA. | 72 hours after OHCA | Death within 72 hours will be counted as the maximum SOFA score (i.e. 24 points). |
| The lower arterial lactate level at day 3 after OHCA. | 72 hours after OHCA | The lower arterial lactate level at day 3 after OHCA. |
Countries
France
Contacts
CONTACTJonathan CHELLY
Outcome results
None listed