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Early high-dose vitamin C for out-of-hospital cardiac arrest: the VITaCCA randomized clinical trial.

  • 2026-06-16
  • Intensive care medicine 52(7)
    • Sander Rozemeijer
    • Eric A Dubois
    • Harm-Jan de Grooth
    • Corstiaan A den Uil
    • Thijs C D Rettig
    • Tom A Rijpstra
    • Bas van den Bogaard
    • Arthur R H van Zanten
    • Rob J Bosman
    • Paul W G Elbers
    • Armand R J Girbes
    • Alexander P J Vlaar
    • Jos W R Twisk
    • Kenneth B Christopher
    • Patrick Schober
    • Heleen M Oudemans-van Straaten
    • Angélique M E de Man

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 273
Population
comatose adults resuscitated from shockable out-of-hospital cardiac arrest
Methods
double-blind, multi-center, phase 2 trial, placebo, 3g or 10g intravenous vitamin C daily for 96 h
Blinding
Double-blind
Duration
96 h
Funding
Unclear
  • Large Human Trial

Background

Besides temperature management, there is currently no effective therapy to decrease the burden of post-cardiac arrest syndrome. The pleiotropic effects of vitamin C may improve clinical outcome.

Purpose

This trial investigated whether early administration of 3 g or 10 g intravenous vitamin C attenuated organ dysfunction post-cardiac arrest.

Methods

In this double-blind, multi-center, phase 2 trial, comatose adults resuscitated from shockable out-of-hospital cardiac arrest randomly received intravenously placebo, supplementary (3 g) or supraphysiological dose (10 g) vitamin C daily for 96 h. The primary endpoint was the 96 h change in the resuscitation-sequential organ failure assessment (R-SOFA) score. Secondary endpoints included neurological outcome, myocardial injury, vasopressor- and ventilator-free days, renal function, ICU-acquired weakness, delirium, length of ICU and hospital stay, and 28- and 180-day mortality.

Results

273 patients (93 on placebo, 91 on 3 g and 89 on 10 g) were included in the primary analysis. Mean (SD) change in R-SOFA score at 96 h was - 3.2 (5.7) in the placebo group, - 2.3 (7.4) in the 3 g group, and - 0.8 (7.6) in the 10 g group (p = 0.04 for overall difference). 10 g vitamin C resulted in 2.5 points less improvement in R-SOFA score compared with placebo (95% CI 0.5-4.5; p = 0.01), and 1.6 points less improvement compared with 3 g vitamin C (95% CI - 0.4 to 3.6; p = 0.12). Vitamin C 10 g led to higher troponin T release, worse renal function and worse neurological outcomes.

Conclusion

In out-of-hospital cardiac arrest patients, intravenous vitamin C did not reduce organ dysfunction at 96 h, but even worsened organ function outcomes in the 10 g group.

Trial registration

NCT03509662.

Research Insights

  • Vitamin C→Improved Neurological Function

    Vitamin C 10 g led to... worse neurological outcomes.

    Effect
    Harmful
    Effect size
    Small
    Dose
    10 g intravenous daily for 96 h
  • Vitamin C→Improved Renal Function

    Vitamin C 10 g led to... worse renal function...

    Effect
    Harmful
    Effect size
    Small
    Dose
    10 g intravenous daily for 96 h
  • Vitamin C→Reduced Myocardial Injury

    Vitamin C 10 g led to higher troponin T release...

    Effect
    Harmful
    Effect size
    Small
    Dose
    10 g intravenous daily for 96 h
  • Vitamin C→Reduced Organ Dysfunction

    10 g vitamin C resulted in 2.5 points less improvement in R-SOFA score compared with placebo (95% CI 0.5-4.5; p=0.01)... Vitamin C 10 g led to... worse organ function...

    Effect
    Harmful
    Effect size
    Small
    Dose
    10 g intravenous daily for 96 h
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