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

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


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: NCT03509662. Registered on April 26, 2018. Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018.