Efficacy of Early Intravenous High-dose Vitamin C in Post-cardiac Arrest Shock.
ConditionCardiac Arrest
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorCentre Hospitalier de Bethune
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
minor or pregnant women;
OHCA from evident extracardiac cause (trauma, bleeding, poisoning, etc.);
Trial design
Design model
Parallel
Treatments tested in this trial
Vitamin C (Laroscorbine) + Vitamin B1 (Bevitine)
Drugin 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.
standard treatment
Drugno 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.
Treatment groups
234 Participants
are divided into 2 treatment groupsGroup A: Control groupActive comparator 1 intervention
Group B: Experimental groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Cumulative incidence of weaning from vasopressors at day 3 after OHCA.
Cumulative incidence of weaning from vasopressors at day 3 after OHCA.
Time frame
day 3Secondary outcomes
1
Cumulative incidence of death by refractory shock within 7 days after OHCA.
Cumulative incidence of death by refractory shock within 7 days after OHCA.
Time frame
day 7 after OHCA2
the neurological outcome at day 28 after OHCA, with mRS range from 0 to 3.
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).
Time frame
day 28 after OHCA3
The maximal vasopressors infusion dose within 3 days after OHCA.
The maximal vasopressors infusion dose within 3 days after OHCA.
Time frame
72 hours after OHCA4
The delta SOFA (sepsis-related organ failure assessment score) is defined as the difference between SOFA admission and SOFA at 72 hours after OHCA.
Death within 72 hours will be counted as the maximum SOFA score (i.e. 24 points).
Time frame
72 hours after OHCASponsors and contacts
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Centre Hospitalier de Bethune
Lead sponsor
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Collaborator
University Hospital, Lille
Collaborator
Source ClinicalTrials.gov