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 - Funding Information: Funding for the VITaCCA-trial was provided by contract to Amsterdam UMC, location VUmc, the study sponsor, by ZonMW (No 848081001). ZonMW will not have any input on the writing and submission of the manuscript, nor will they have any input on the writing of future manuscripts or decisions to publish data acquired in relation to this study. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
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/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.
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/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.
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 - http://www.scopus.com/inward/record.url?scp=85112745053&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13063-021-05483-3
DO - https://doi.org/10.1186/s13063-021-05483-3
M3 - Article
C2 - 34407846
SN - 1745-6215
VL - 22
SP - 546
JO - Trials
JF - Trials
IS - 1
M1 - 546
ER -