Tomoko Fujii1, Andrew A Udy2, Adam M Deane3, Nora Luethi2, Michael Bailey2, Glenn M Eastwood2, Daniel Frei4, Craig French2, Neil Orford2, Yahya Shehabi5, Paul J Young6, Rinaldo Bellomo2. 1. Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia. Tomoko.Fujii@monash.edu. 2. Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 3. Department of Intensive Care, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. 4. Department of Anaesthesia and Pain Medicine, Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand. 5. Critical Care and Perioperative Services, Monash Health, Monash University, Melbourne, VIC, Australia. 6. Intensive Care Unit, Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand.
Abstract
BACKGROUND: Septic shock is associated with poor outcomes. Vitamin C (ascorbic acid) is a cellular antioxidant and has anti-inflammatory properties. Whether the combination therapy of vitamin C, thiamine and hydrocortisone reduces vasopressor dependency in septic shock is unclear. OBJECTIVES: To describe the protocol and statistical analysis plan of a multicentre, open-label, prospective, phase 2 randomised clinical trial evaluating the effects of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone monotherapy on the duration of vasopressor administration in critically ill patients with septic shock. METHODS: VITAMINS is a multicentre cardiovascular efficacy trial in adult patients with septic shock. Randomisation occurs via a secure website with stratification by site, and allocation concealment is maintained throughout the trial. The primary outcome is the duration of time alive and free of vasopressor administration at Day 7. Secondary outcomes include feasibility endpoints and some patientcentred outcomes. All analyses will be conducted on an intention-to-treat basis. CONCLUSION: The VITAMINS trial will determine whether combination therapy of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone increases vasopressor-free hours in critically ill patients with septic shock. The conduct of this study will provide important information on the feasibility of studying this intervention in a phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov, identification No. NCT03333278.
RCT Entities:
BACKGROUND:Septic shock is associated with poor outcomes. Vitamin C (ascorbic acid) is a cellular antioxidant and has anti-inflammatory properties. Whether the combination therapy of vitamin C, thiamine and hydrocortisone reduces vasopressor dependency in septic shock is unclear. OBJECTIVES: To describe the protocol and statistical analysis plan of a multicentre, open-label, prospective, phase 2 randomised clinical trial evaluating the effects of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone monotherapy on the duration of vasopressor administration in critically illpatients with septic shock. METHODS:VITAMINS is a multicentre cardiovascular efficacy trial in adult patients with septic shock. Randomisation occurs via a secure website with stratification by site, and allocation concealment is maintained throughout the trial. The primary outcome is the duration of time alive and free of vasopressor administration at Day 7. Secondary outcomes include feasibility endpoints and some patientcentred outcomes. All analyses will be conducted on an intention-to-treat basis. CONCLUSION: The VITAMINS trial will determine whether combination therapy of vitamin C, thiamine and hydrocortisone when compared with hydrocortisone increases vasopressor-free hours in critically illpatients with septic shock. The conduct of this study will provide important information on the feasibility of studying this intervention in a phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov, identification No. NCT03333278.
Authors: Ryan Gardner; Xiaowen Liu; Yanbo Wang; Andrew Cole; Stanley Heydrick; Michael W Donnino; Ari Moskowitz Journal: Resuscitation Date: 2020-09-16 Impact factor: 5.262
Authors: Tomoko Fujii; Nora Luethi; Paul J Young; Daniel R Frei; Glenn M Eastwood; Craig J French; Adam M Deane; Yahya Shehabi; Ludhmila A Hajjar; Gisele Oliveira; Andrew A Udy; Neil Orford; Samantha J Edney; Anna L Hunt; Harriet L Judd; Laurent Bitker; Luca Cioccari; Thummaporn Naorungroj; Fumitaka Yanase; Samantha Bates; Forbes McGain; Elizabeth P Hudson; Wisam Al-Bassam; Dhiraj Bhatia Dwivedi; Chloe Peppin; Phoebe McCracken; Judit Orosz; Michael Bailey; Rinaldo Bellomo Journal: JAMA Date: 2020-02-04 Impact factor: 56.272
Authors: David C Consoli; Jordan J Jesse; Kelly R Klimo; Adriana A Tienda; Nathan D Putz; Julie A Bastarache; Fiona E Harrison Journal: Nutrients Date: 2020-03-26 Impact factor: 5.717