TY - JOUR
T1 - Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA)
T2 - study protocol for a randomized, double-blind, multi-center, placebo-controlled trial
AU - Rozemeijer, Sander
AU - de Grooth, Harm Jan
AU - Elbers, Paul W.G.
AU - Girbes, Armand R.J.
AU - den Uil, Corstiaan A.
AU - Dubois, Eric A.
AU - Wils, Evert Jan
AU - Rettig, Thijs C.D.
AU - van Zanten, Arthur R.H.
AU - Vink, Roel
AU - van den Bogaard, Bas
AU - Bosman, Rob J.
AU - Oudemans-van Straaten, Heleen M.
AU - de Man, Angélique M.E.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/8/18
Y1 - 2021/8/18
N2 - 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://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL
AB - 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://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL
KW - Ascorbic acid
KW - Cardiac arrest
KW - Free radicals
KW - Ischemia/reperfusion injury
KW - Out-of-hospital cardiac arrest
KW - Oxidative stress
KW - Post-cardiac arrest syndrome
KW - Reactive oxygen species
KW - Vitamin C
UR - https://doi.org/10.6084/m9.figshare.c.5568588
U2 - 10.1186/s13063-021-05483-3
DO - 10.1186/s13063-021-05483-3
M3 - Article
AN - SCOPUS:85112745053
VL - 22
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 546
ER -