Clinical trial NCT05817851: Efficacy of Early Intravenous High-dose Vitamin C in Post-cardiac Arrest Shock.
Official title: Efficacy of Early Intravenous High-dose Vitamin C in Post-cardiac Arrest Shock: a Multicenter, Randomized Controled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cardiac Arrest
Lead sponsor: Centre Hospitalier de Bethune
Sponsor class: NETWORK
Collaborators: name: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
name: University Hospital, Lille
First posted: 2023-04-18
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Exclusion criteria:

* minor or pregnant women;
* OHCA from evident extracardiac cause (trauma, bleeding, poisoning, etc.);
* interval between RACS and randomization \> 6 hours;
* extracorporeal circulatory assistance requirement in the first 4 hours after OHCA;
* history of urolithiasis, oxalate nephropathy or hemochromatosis;
* glucose-6-phosphate deshydrogenase deficiency; nephrolithiasis, hyperoxalyurie
* patients already treated with vit-C; known vit-C deficit;
* inclusion in another study;
* pre-existent severe chronic kidney disease (glomerular filtration rate \< 30ml/min);
* treatment limitationsor moribound
* Patient with derpived freedom or with legal protective measures.
* Patient not covered by French national health insurance

Primary outcomes:
measure: Cumulative incidence of weaning from vasopressors at day 3 after OHCA.
timeFrame: day 3
Secondary outcomes:
measure: Cumulative incidence of death by refractory shock within 7 days after OHCA.
timeFrame: day 7 after OHCA
measure: the neurological outcome at day 28 after OHCA, with mRS range from 0 to 3.
timeFrame: day 28 after OHCA
measure: The maximal vasopressors infusion dose within 3 days after OHCA.
timeFrame: 72 hours after OHCA
measure: The delta SOFA (sepsis-related organ failure assessment score) is defined as the difference between SOFA admission and SOFA at 72 hours after OHCA.
timeFrame: 72 hours after OHCA
measure: The lower arterial lactate level at day 3 after OHCA.
timeFrame: 72 hours after OHCA
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Béthune
country: France
facility: Centre Hospitalier Béthune
city: Dieppe
country: France
facility: Centre Hospitalier de Dieppe
city: Jossigny
country: France
facility: GHEF Site Marne La Vallée
city: Lens
country: France
facility: Centre Hospitalier de LENS
city: Lille
country: France
facility: Centre Hospitalier Universitaire de LILLE
city: Paris
country: France
facility: Hôpital Lariboisière
city: Rouen
country: France
facility: Centre Hospitalier de Rouen
city: Toulon
country: France
facility: Centre Hospitalier Toulon La Seyne sur Mer
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
Study officials:
References: