The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial

血液透析 医学 肝素 透析 安慰剂 凝血时间激活 内科学 外科 泌尿科 不利影响 病理 替代医学
作者
Christina U. Lorentz,Erik I. Tucker,Norah G. Verbout,Joseph J. Shatzel,Sven R. Olson,Brandon D. Markway,Michael Wallisch,Martina Ralle,Monica T. Hinds,Owen J. T. McCarty,David Gailani,Jeffrey I. Weitz,András Gruber
出处
期刊:Blood [American Society of Hematology]
卷期号:138 (22): 2173-2184 被引量:40
标识
DOI:10.1182/blood.2021011725
摘要

Abstract End-stage renal disease (ESRD) patients on chronic hemodialysis have repeated blood exposure to artificial surfaces that can trigger clot formation within the hemodialysis circuit. Dialyzer clotting can lead to anemia despite erythropoietin and iron supplementation. Unfractionated heparin prevents clotting during hemodialysis, but it is not tolerated by all patients. Although heparin-free dialysis is performed, intradialytic blood entrapment can be problematic. To address this issue, we performed a randomized, double-blind, phase 2 study comparing AB023, a unique antibody that binds factor XI (FXI) and blocks its activation by activated FXII, but not by thrombin, to placebo in 24 patients with ESRD undergoing heparin-free hemodialysis. Patients were randomized to receive a single predialysis dose of AB023 (0.25 or 0.5 mg/kg) or placebo in a 2:1 ratio, and safety and preliminary efficacy were compared with placebo and observations made prior to dosing within each treatment arm. AB023 administration was not associated with impaired hemostasis or other drug-related adverse events. Occlusive events requiring hemodialysis circuit exchange were less frequent and levels of thrombin-antithrombin complexes and C-reactive protein were lower after AB023 administration compared with data collected prior to dosing. AB023 also reduced potassium and iron entrapment in the dialyzers, consistent with less blood accumulation within the dialyzers. We conclude that despite the small sample size, inhibition of contact activation–induced coagulation with AB023 was well tolerated and reduced clotting within the dialyzer. This trial was registered at www.clinicaltrials.gov as #NCT03612856.
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