{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:06:15Z","timestamp":1779782775226,"version":"3.53.1"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430012010010"],"award-info":[{"award-number":["10430012010010"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Kallikrein\u2010kinin system (KKS) dysregulation is hypothesized to play a pathogenetic role in COVID\u201019\u2010associated pulmonary oedema. To investigate the efficacy and safety of intravenous lanadelumab, a monoclonal antibody that inhibits plasma kallikrein, in COVID\u201019, we conducted a phase 2, open\u2010label, randomized\u2010controlled, proof\u2010of\u2010concept, interventional trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We recruited 40 patients hospitalized with moderate COVID\u201019 and randomized them 1:1 to receive either standard\u2010of\u2010care (SoC) treatment or SoC plus intravenous lanadelumab (300\u2009mg on days one and four). The primary outcome consisted of repeated measurements of supplemental oxygen (litres\/minute) necessary to maintain a peripheral oxygen saturation (SpO\n                      <jats:sub>2<\/jats:sub>\n                      )\u2009\u2265\u200993%. Secondary outcomes included modified WHO\u2010CPS scores, need for high\u2010flow oxygen therapy or mechanical ventilation, admission to the intensive care unit, length of hospital stay and all\u2010cause mortality over a 14\u2010day period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sufficient endpoint data for the population were available for the first five days, but not for the previsioned 14\u2010day endpoint. Consequently, analysis of the primary endpoint was based on the first five days of treatment. Within this timeframe, lanadelumab did not significantly affect supplemental oxygen volumes. Neither treatment nor interaction between treatment and time was a significant predictor of oxygen volumes in a linear mixed model (p\u2009=\u20090.49 and p\u2009=\u20090.15, respectively). None of the secondary outcomes was significantly affected by lanadelumab. Intravenous lanadelumab was well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This exploratory study was evaluated using a shortened primary endpoint period. Lanadelumab showed no indication of benefit on oxygen needs or other clinical outcomes in patients with COVID\u201019. Lanadelumab was well tolerated throughout the trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70438","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T08:31:44Z","timestamp":1767947504000},"page":"1685-1695","source":"Crossref","is-referenced-by-count":0,"title":["Intravenous lanadelumab for the treatment of moderately ill COVID\u201019 patients"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-598X","authenticated-orcid":false,"given":"Job J.","family":"Engel","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Radboud Centre for Infectious Diseases Radboudumc  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"van Linge","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Molecular Medicine (CEMM) and Division of Infectious Diseases, Amsterdam University Medical Centres Amsterdam University Medical Centres\u2010 Location AMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Joost","family":"Wiersinga","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Molecular Medicine (CEMM) and Division of Infectious Diseases, Amsterdam University Medical Centres Amsterdam University Medical Centres\u2010 Location AMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse J. E.","family":"Kouijzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Centre for Infectious Diseases Radboudumc  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quirijn","family":"de Mast","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Centre for Infectious Diseases Radboudumc  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u2010Jan","family":"Hassing","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Rijnstate Hospital  Arnhem the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danique J. H.","family":"Huijbens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Rijnstate Hospital  Arnhem the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen L.","family":"Leavis","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University Medical Centre Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Schutgens","sequence":"additional","affiliation":[{"name":"Centre for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek University Medical Centre Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen","family":"Maas","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory University Medical Centre Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kit C. B.","family":"Roes","sequence":"additional","affiliation":[{"name":"Department of Health Evidence, Section Biostatistics Radboudumc, Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank L.","family":"van de Veerdonk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Centre for Infectious Diseases Radboudumc  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-725X","authenticated-orcid":false,"given":"Roger","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Radboudumc Institute for Health Sciences Radboudumc  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(21)00218\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57555"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02014"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.10.025"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13194"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13235"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16176"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.909342"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104195"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.627579"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200581200"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00498.2016"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408\u2010020\u201000408\u20104"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010145"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1522"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2165\/11204500\u2010000000000\u201000000"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12806"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1605767"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.16773"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.17708"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac984"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1R423"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000441060"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.138"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102021\u2010060664"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(22)00006\u20106"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000603\u20106"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.297"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01061"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3379"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac632"},{"key":"e_1_2_11_36_1","unstructured":"The Dutch Working Party on Antibiotic Policy (Stichting Werkgroep AntibioticaBeleid S.Medicamenteuze behandeling voor pati\u00ebnten met COVID\u201019 The Dutch Federation of Medical Specialists (Federatie Medisch Specialisten FMS). 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