{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:43:38Z","timestamp":1777452218827,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["11220506"],"award-info":[{"award-number":["11220506"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology Case Reports"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A pilot study to assess the feasibility of a randomization trial protocol comparing low (2.5\u2009mg) and standard (10\u2009mg) doses of intrapleural tissue plasminogen activator (tPA) with deoxyribonucleases (DNase) in unresolved pleural infection. The proposed protocol comparing low\u2010dose and standard doses of intrapleural tPA (with DNase) therapy will be feasible and acceptable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A single\u2010centre, two\u2010arm, double\u2010blinded, randomised controlled feasibility study which includes subjects with unresolved pleural infection eligible for intrapleural tPA\/DNase injection, with follow\u2010ups till 3\u2009months after hospital discharge. Recruited subjects will be randomised in a 1:1 ratio to receive a maximum of 6 doses of intrapleural tPA (with DNase) starting at either 2.5 or 10\u2009mg. A clinical decision is allowed at or after the third dose of tPA to continue the assigned regimen (blinded) or convert to open\u2010label use of 10\u2009mg doses of tPA to complete the course based on the clinical response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The main outcome is the feasibility of the trial protocol, based on the percentage of eligible patients enrolled, retained to discharge, and completing 3\u2009months of follow\u2010up. Other important outcomes include survival at 3\u2009months follow\u2010up and without the need for surgical intervention, the need for additional pleural interventions, the number of decisions to convert to open\u2010labelled use of 10\u2009mg intrapleural tPA, clinical and radiographic response after the treatment course, safety profiles, especially bleeding complications and the number and reason for protocol violation. Feasibility outcomes will be reported as descriptive data. Comparison of outcomes between the two treatment groups will be analysed on an intention\u2010to\u2010treat basis. Safety outcomes will be reported descriptively for each group. The reported estimates of recruitment rates, adherence, follow\u2010up completeness, and variability and event rates for key clinical and bleeding outcomes will inform the design of future studies that incorporate the current study design.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial registration:<\/jats:bold>\n                      NCT05766124,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05766124\">ClinicalTrials.gov<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcr2.70580","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T09:56:19Z","timestamp":1775296579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Parallel Group, 1:1 Randomised, Pilot Study Comparing the Clinical Efficacy and Bleeding Risk Between Low Dose and Standard Dose Intrapleural Tissue Plasminogen Activator for Adults With Pleural Infection"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8163-5846","authenticated-orcid":false,"given":"Ken Ka Pang","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Medicine &amp; Therapeutics, Faculty of Medicine Chinese University of Hong Kong  Hong Kong China"},{"name":"Li Ka Shing Institute of Health Science, Faculty of Medicine Chinese University of Hong Kong  Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-9232","authenticated-orcid":false,"given":"Christopher","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine &amp; Therapeutics, Faculty of Medicine Chinese University of Hong Kong  Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Shu Cheong","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Medicine &amp; Therapeutics, Faculty of Medicine Chinese University of Hong Kong  Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8956-0537","authenticated-orcid":false,"given":"Ai Ling","family":"Tan","sequence":"additional","affiliation":[{"name":"Centre for Innovative Pleural Research, Sir Charles Gairdner Hospital  Perth Australia"},{"name":"Pleural Medicine Unit Institute for Respiratory Health  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-511X","authenticated-orcid":false,"given":"Y. C. Gary","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for Innovative Pleural Research, Sir Charles Gairdner Hospital  Perth Australia"},{"name":"Pleural Medicine Unit Institute for Respiratory Health  Perth Australia"},{"name":"Department of Respiratory Medicine Sir Charles Gairdner Hospital  Perth Australia"},{"name":"School of Medicine, University of Western Australia  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Centre for Health Protection \u201cDeath Rate by Leading Cause of Death 2001\u20132024 \u201daccessed February 14 2023 https:\/\/www.chp.gov.hk\/en\/statistics\/data\/10\/27\/117.html."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12658"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-1558"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2016.07.030"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e328352c673"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042473"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012740"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.99.2.270"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201407-329OC"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00084-2019"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000487"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-015-9807-6"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201609-673OC"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.14261"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcr2.408"},{"issue":"1","key":"e_1_2_12_17_1","first-page":"00590","article-title":"An International Survey on the Use of Intrapleural Tissue Plasminogen Activator\/DNase Therapy for Pleural Infection","volume":"8","author":"Lau E. 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