Department of Cardiothoracic Surgery, Jena University Hospital - Friedrich Schiller University of Jena, Jena, Thuringia, Germany.
Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Thuringia, Germany.
BMJ Open. 2020 Mar 30;10(3):e031912. doi: 10.1136/bmjopen-2019-031912.
Infective endocarditis (IE) is associated with high mortality and morbidity. Multiple organ failure is the main cause of death after surgery for IE. Cardiopulmonary bypass (CPB) can cause a systemic inflammatory response. In a pilot study (REMOVE-pilot (Revealing mechanisms and investigating efficacy of hemoad-sorption for prevention of vasodilatory shock in cardiac surgery patients with infective endocarditis - a multicentric randomized controlled group sequential trial)), we found that plasma profiles of cytokines during and after CPB were higher in patients with IE compared with patients with non-infectious valvular heart disease. Sequential Organ Failure Assessment (SOFA) scores on the first and second postoperative days and in-hospital mortality were also higher in IE patients. This protocol describes the design of the REMOVE trial on cytokine-adsorbing columns, for example, CytoSorb, for non-selective removal of cytokines. The aim of the REMOVE study is to demonstrate efficacy of CytoSorb on the prevention of multiorgan dysfunction in patients with IE undergoing cardiac surgery.
The REMOVE study is an interventional randomised controlled multicenter trial with a group sequential (Pocock) design for assessing efficacy of CytoSorb in patients undergoing cardiac surgery for IE. The change in mean total SOFA (∆ SOFA) score between preoperative and postoperative care will be used as primary endpoint. Data on 30-day mortality, changes in cytokines levels, duration of mechanical ventilation, length of intensive care unit and hospital stay, and postoperative stroke will be collected as secondary endpoints. An interim analysis will be conducted after including 25 participating patients per study arm (with a focus on feasibility of the recruitment as well as differences in cytokines and cell-free DNA levels).
The protocol was approved by the institutional review board and ethics committee of the University of Jena as well as by the corresponding ethics committee of each participating study centre. The results will be published in a renowned international medical journal, irrespective of the outcomes of the study.
The ClinicalTrials.gov registry (NCT03266302).
感染性心内膜炎（IE）与高死亡率和高发病率相关。多器官衰竭是 IE 手术后死亡的主要原因。体外循环（CPB）可引起全身炎症反应。在一项初步研究（REMOVE-初步研究（揭示心脏手术患者感染性心内膜炎中血液吸附预防血管扩张性休克的机制和疗效的研究-一项多中心随机对照分组序贯试验））中，我们发现 CPB 期间和之后的细胞因子血浆谱在 IE 患者中高于非感染性瓣膜性心脏病患者。IE 患者术后第 1 天和第 2 天的序贯器官衰竭评估（SOFA）评分和住院死亡率也较高。本方案描述了用于非选择性清除细胞因子的细胞因子吸附柱（例如 CytoSorb）的 REMOVE 试验设计。REMOVE 研究的目的是证明 CytoSorb 在预防接受心脏手术的 IE 患者多器官功能障碍方面的疗效。
REMOVE 研究是一项干预性随机对照多中心试验，采用分组序贯（Pocock）设计评估 CytoSorb 在 IE 患者心脏手术中的疗效。术前和术后护理之间平均总 SOFA（∆SOFA）评分的变化将作为主要终点。将 30 天死亡率、细胞因子水平变化、机械通气时间、重症监护病房和住院时间以及术后中风的数据作为次要终点收集。在每个研究组纳入 25 名参与患者（重点关注招募的可行性以及细胞因子和无细胞 DNA 水平的差异）后将进行中期分析。
该方案已获得耶拿大学机构审查委员会和伦理委员会以及每个参与研究中心的相应伦理委员会的批准。研究结果将发表在著名的国际医学期刊上，无论研究结果如何。
ClinicalTrials.gov 注册表（NCT03266302）。
