Treatment Effects of Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest (The IMICA Trial)

作者：M Meyer, Sebastian C. Wiberg, Johannes Grand, Anna Sina P. Meyer, Laust Emil Roelsgaard Obling, Martin Steen Frydland, Jakob Hartvig Thomsen, Jakob Josiassen, Jacob Eifer Møller, Jesper Kjærgaard, Christian Hassager · 发表于：Circulation · 年份：2021 · DOI：10.1161/circulationaha.120.053318 · 被引用次数：136 · 研究领域：Cardiac Arrest and Resuscitation、Sepsis Diagnosis and Treatment、Immune Response and Inflammation

Background: Patients experiencing out-of-hospital cardiac arrest who remain comatose after initial resuscitation are at high risk of morbidity and mortality attributable to the ensuing post–cardiac arrest syndrome. Systemic inflammation constitutes a major component of post–cardiac arrest syndrome, and IL-6 (interleukin-6) levels are associated with post–cardiac arrest syndrome severity. The IL-6 receptor antagonist tocilizumab could potentially dampen inflammation in post–cardiac arrest syndrome. The objective of the present trial was to determine the efficacy of tocilizumab to reduce systemic inflammation after out-of-hospital cardiac arrest of a presumed cardiac cause and thereby potentially mitigate organ injury. Methods: Eighty comatose patients with out-of-hospital cardiac arrest were randomly assigned 1:1 in a double-blinded placebo-controlled trial to a single infusion of tocilizumab or placebo in addition to standard of care including targeted temperature management. Blood samples were sequentially drawn during the initial 72 hours. The primary end point was the reduction in C-reactive protein response from baseline until 72 hours in patients treated with tocilizumab evaluated by mixed-model analysis for a treatment-by-time interaction. Secondary end points (main) were the marker of inflammation: leukocytes; the markers of myocardial injury: creatine kinase myocardial band, troponin T, and N-terminal pro B-type natriuretic peptide; and the marker of brain injury: neu...