Efficacy of Early Intravenous High-dose Vitamin C in Post-cardiac Arrest Shock. (VICEPAC)

Centre Hospitalier de Bethune

Status and phase: Enrolling; Phase 2

Conditions: Cardiac Arrest

Treatments: Drug: standard treatment; Drug: Vitamin C (Laroscorbine) + Vitamin B1 (Bevitine)

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT05817851

2022-01

Details and patient eligibility

About

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

Enrollment: 234 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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234 participants in 2 patient groups

Control group

Active Comparator group

Description:

- Control group (standard treatment): post-cardiac arrest care will be provided, including temperature control, according to current international guidelines and local procedures. 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:

Drug: standard treatment

Experimental group

Experimental group

Description:

- Experimental group (IV high-dose vit-C): 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.

Treatment:

Drug: Vitamin C (Laroscorbine) + Vitamin B1 (Bevitine)