Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial

Sander Rozemeijer, Harm-Jan de Grooth, Paul W G Elbers, Armand R J Girbes, Corstiaan A den Uil, Eric A Dubois, Evert-Jan Wils, Thijs C D Rettig, Arthur R H van Zanten, Roel Vink, Bas van den Bogaard, Rob J Bosman, Heleen M Oudemans-van Straaten, Angélique M E de Man, Sander Rozemeijer, Harm-Jan de Grooth, Paul W G Elbers, Armand R J Girbes, Corstiaan A den Uil, Eric A Dubois, Evert-Jan Wils, Thijs C D Rettig, Arthur R H van Zanten, Roel Vink, Bas van den Bogaard, Rob J Bosman, Heleen M Oudemans-van Straaten, Angélique M E de Man

Abstract

Background: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients.

Methods: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations.

Discussion: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest.

Trial registration: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://ichgcp.net/clinical-trials-registry/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.

Keywords: Ascorbic acid; Cardiac arrest; Free radicals; Ischemia/reperfusion injury; Out-of-hospital cardiac arrest; Oxidative stress; Post-cardiac arrest syndrome; Reactive oxygen species; Vitamin C.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart of the study protocol
Fig. 2
Fig. 2
Data collection and follow-up of the participants in the VITaCCA-trial (SPIRIT figure)

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