Raman Sainath, Gibbons Kristen S, Jayashree Muralidharan, Lalitha A V, Bellomo Rinaldo, Blythe Robin, Buckley David, Butt Warwick, Cho Hwa Jin, Cree Michele, de Souza Daniela C, Erickson Simon, Festa Marino, Ganu Subodh, George Shane, James Ebor Jacob, Johnson Kerry, Le Marsney Renate, Lister Paula, Pham Trang M T, Singh Puneet, Venkatesh Balasubramanian, Wall Renee, Long Debbie A, Schlapbach Luregn J
Children's Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Paediatric Intensive Care Unit, Queensland Children's Hospital, South Brisbane, QLD, Australia.
Pediatr Crit Care Med. 2025 Mar 1;26(3):e374-e385. doi: 10.1097/PCC.0000000000003674. Epub 2024 Dec 26.
Pediatric sepsis results in significant morbidity and mortality worldwide. There is an urgent need to investigate adjunctive therapies that can be administered early. We hypothesize that using vitamin C combined with hydrocortisone increases survival free of inotropes/vasopressors support until day 7 compared with standard care. Here we describe the Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial protocol, which aims to address this hypothesis.
Randomized, open label, controlled, parallel-group, three-arm trial with integrated economic evaluation.
Nine Australia and New Zealand PICUs, with interest from additional international sites.
Children between 7 days and younger than 18 years old who are treated for suspected or confirmed sepsis and receiving inotropes/vasopressors for greater than 1 hour.
IV vitamin C (100 mg/kg [maximum 5 g] every 6 hr) and hydrocortisone (1 mg/kg [maximum 50 mg] every 6 hr), or IV hydrocortisone alone (1 mg/kg [maximum 50 mg] every 6 hr) or standard care.
Three hundred eighty-four children will be randomly assigned to receive the interventions, or standard care in a 1:1:1 ratio with stratification by steroid administration pre-randomization and hospital site. The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days. Secondary outcomes include 28-day mortality, survival free of organ support, PICU length of stay, quality of life, functional status and neurodevelopmental vulnerability at 6 months post-enrollment, and hospitalization-related costs. Statistical analysis will be based on an intention-to-treat principle. The study has ethical approval (HREC/20/QCHQ/69922, dated December 21, 2020), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621000247875), commenced recruitment on December 8, 2021, and is expected to finish recruitment by mid-2026.
Dissemination of the results will occur through publication in peer-reviewed journals, presentations at international conferences, and additional consumer-informed pathways.
小儿脓毒症在全球范围内导致了显著的发病率和死亡率。迫切需要研究能够早期应用的辅助治疗方法。我们假设，与标准治疗相比，使用维生素C联合氢化可的松可提高在第7天前无需使用血管活性药物支持的生存率。在此，我们描述了使用维生素C和氢化可的松进行小儿脓毒性休克复苏（RESPOND）试验方案，旨在验证这一假设。
随机、开放标签、对照、平行组、三臂试验，并进行综合经济评估。
澳大利亚和新西兰的9个儿科重症监护病房，其他国际机构也感兴趣。
年龄在7天至18岁以下，因疑似或确诊脓毒症接受治疗且使用血管活性药物超过1小时的儿童。
静脉注射维生素C（每6小时100mg/kg[最大5g]）和氢化可的松（每6小时1mg/kg[最大50mg]），或单独静脉注射氢化可的松（每6小时1mg/kg[最大50mg]）或标准治疗。
384名儿童将按1:1:1的比例随机分配接受干预措施或标准治疗，随机分组前根据是否使用类固醇以及医院地点进行分层。主要结局指标是存活且无需使用血管活性药物的时间，在第7天进行截尾。次要结局指标包括28天死亡率、无需器官支持的生存率、儿科重症监护病房住院时间、生活质量、功能状态以及入组后6个月时的神经发育易损性，还有住院相关费用。统计分析将基于意向性分析原则。该研究已获得伦理批准（HREC/20/QCHQ/69922，日期为2020年12月21日），已在澳大利亚新西兰临床试验注册中心注册（ACTRN12621000247875），于2021年12月8日开始招募，预计2026年年中完成招募。
研究结果将通过在同行评审期刊上发表、在国际会议上报告以及其他面向公众的途径进行传播。
