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

Efficacy of Early Intravenous High-dose Vitamin C in Post-cardiac Arrest Shock: a Multicenter, Randomized Controled 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

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest
• Intervention / Treatment: Drug: standard treatment; Drug: Vitamin C (Laroscorbine) + Vitamin B1 (Bevitine)

• Study Type: Interventional
• Enrollment (Estimated): 234
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christophe VINSONNEAU; Phone Number: 03.21.64.44.44; Email: cvinsonneau@ch-bethune.fr
• Study Contact Backup: Name: Jonathan CHELLY

Study Locations

• France
  • Amiens, France
    • Active, not recruiting
    • Centre Hospitalier Universitaire d'Amiens
  • Béthune, France, 62408
    • Active, not recruiting
    • Centre Hospitalier Béthune
  • Dieppe, France
    • Active, not recruiting
    • Centre Hospitalier de Dieppe
  • Jossigny, France
    • Active, not recruiting
    • GHEF Site Marne La Vallée
  • Lens, France, 62307
    • Not yet recruiting
    • Centre Hospitalier de LENS
    • Contact: MELANIE VERLAY; Phone Number: 0601023068; Email: mverlay@ch-lens.fr
    • Principal Investigator: Olivier NIGEON
  • Lille, France
    • Recruiting
    • Centre Hospitalier Universitaire de Lille
    • Principal Investigator: Patrick GIRARDIE, Dr
  • Rouen, France
    • Active, not recruiting
    • Centre Hospitalier de Rouen
  • Toulon, France
    • Recruiting
    • Centre Hospitalier Toulon La Seyne sur Mer
    • Principal Investigator: Jonathan CHELLY
  • Valenciennes, France
    • Active, not recruiting
    • Centre hospitalier de valenciennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

• nclusion 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; - 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.	Drug: standard 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.
Experimental: Experimental group; - 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.	Drug: Vitamin 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.; Other Names: Laroscorbine + Bevitine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of weaning from vasopressors at day 3 after OHCA.	Cumulative incidence of weaning from vasopressors at day 3 after OHCA.	day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of death by refractory shock within 7 days after OHCA.	Cumulative incidence of death by refractory shock within 7 days after OHCA.	day 7 after OHCA
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).	day 28 after OHCA
The maximal vasopressors infusion dose within 3 days after OHCA.	The maximal vasopressors infusion dose within 3 days after OHCA.	72 hours 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.	Death within 72 hours will be counted as the maximum SOFA score (i.e. 24 points).	72 hours after OHCA
The lower arterial lactate level at day 3 after OHCA.	The lower arterial lactate level at day 3 after OHCA.	72 hours after OHCA

Collaborators and Investigators

• Sponsor: Centre Hospitalier de Bethune
• Collaborators: University Hospital, Lille; Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): January 24, 2026

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: April 5, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Physiological Effects of Drugs; Micronutrients; Vitamin B Complex; Vitamins; Thiamine
• Other Study ID Numbers: 2022-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No