4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Intensive Care Medicine, Radboudumc, Nijmegen, The Netherlands.
BMJ Open. 2022 Dec 20;12(12):e067251. doi: 10.1136/bmjopen-2022-067251.
Sepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.
ImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation.
The protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d'éthique de la recherche sur l'être human of Switzerland. The results will be submitted for publication in peer-reviewed journals.
NCT04990232.
败血症是住院患者死亡的主要原因。越来越多的证据表明，败血症级联反应中的免疫反应处于宿主反应失调的范围内。在该范围内的一端是反应特征为爆发性过度炎症或巨噬细胞活化样综合征（MALS）的患者，而在另一端是免疫反应特征为免疫麻痹的患者。相当一部分患者处于这两个极端之间。为了为每位患者选择合适的免疫治疗方法，从而提高改善预后的机会，识别免疫表型非常重要。
ImmunoSep 是一项随机、安慰剂对照的 2 期临床试验，采用双盲设计，研究了精准免疫疗法对 MALS 和免疫麻痹败血症表型的影响。患者使用生物标志物进行分层。具体来说，280 名患者将以 1:1 的比例随机分为安慰剂组或标准治疗加活性免疫治疗组。在活性免疫治疗组中，MALS 患者将静脉内给予 anakinra（重组白细胞介素-1 受体拮抗剂），免疫麻痹患者将皮下给予重组人干扰素-γ。主要终点是随机分组后第 9 天，平均总序贯器官衰竭评估评分至少下降 1.4 分。
该方案已获得德国联邦药物和医疗器械研究所；希腊国家伦理委员会和希腊国家药品管理局；荷兰中央人体研究伦理委员会和 Oost Netherland METC；罗马尼亚国家药品和医疗器械管理局；以及瑞士瑞士联邦公共卫生署的批准。结果将提交给同行评议期刊发表。
NCT04990232。
