Anti-CD14 Treatment in Patients With Severe COVID-19 Clinical and Biological Effects in a Phase 2 Randomized Open-Label Adaptive Platform Clinical Trial

作者：F. Linzee Mabrey, Thomas R. Martin, Carolyn S. Calfee, Kathleen D. Liu, Benjamín Lacombe, Lamorna Brown Swigart, Andrea Discacciati, Martin Eklund, Susan R. Heckbert, Michael A. Matthay, Laura J. Esserman, Mark M. Wurfel · 发表于：CHEST Critical Care · 年份：2024 · DOI：10.1016/j.chstcc.2024.100117 · 被引用次数：4 · 研究领域：Immune Response and Inflammation、Cell Adhesion Molecules Research、COVID-19 Clinical Research Studies

Background Cluster of differentiation 14 (CD14)-dependent innate immunity contributes to poor outcomes in COVID-19 pneumonia. Research Question What are the clinical and biological effects of a blocking anti-CD14 monoclonal antibody (IC14) for treatment of severe COVID-19 pneumonia and what is the usefulness of a biomarker of CD14 pathway activation in predicting outcome? Study Design And Methods We report a preplanned secondary analysis of the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis to Coronavirus Disease of 2019 (I-SPY COVID) trial, which enrolled hospitalized patients with severe COVID-19 pneumonia who required high-level respiratory support at 19 medical centers in the United States. Participants were randomized to receive either IV IC14 (4 mg/kg on day 1, then 2 mg/kg on days 2-4; n = 67) or standard care (n = 76). Primary end points included time to recovery, defined as the first 2-day period with ≤ 6 L/min of oxygen, and mortality. In predefined secondary analyses, we tested the association between IC14 treatment and mortality in patients with high or low baseline plasma presepsin, a biomarker of CD14 pathway activity, and the effects of IC14 on plasma biomarkers of pharmacodynamics, injury, and inflammation. Results IC14 treatment did not improve time to recovery or 28-day mortality in the overall population, and the trial was stopped because of meeting futility criteria for the time-to-recovery end poin...