Early high-dose vitamin C for out-of-hospital cardiac arrest: the VITaCCA randomized clinical 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. Visual abstract: (Figure presented.)