• Eleanor K Mishra, Amelia O Clive, Genevieve H Wills, Helen E Davies, Andrew E Stanton, Mohamed Al-Aloul, Alan Hart-Thomas, Justin Pepperell, Matthew Evison, Tarek Saba, Richard Neil Harrison, Anur Guhan, Matthew E Callister, Ramamurthy Sathyamurthy, Sunita Rehal, John P Corcoran, Robert Hallifax, Ioannis Psallidas, Nicky Russell, Rachel Shaw, Melissa Dobson, John M Wrightson, Alex West, Lee Y C Gary YCG 0000-0002-0036-511X 16 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; and., Andrew J Nunn, Robert F Miller, Nick A Maskell, and Najib M Rahman.
• 1 Norfolk and Norwich Pleural Unit, Norfolk and Norwich University Hospital NHS Foundation Trust, Norfolk, United Kingdom.
• Am. J. Respir. Crit. Care Med. 2018 Feb 15; 197 (4): 502-508.

RationalePatients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage.ObjectivesTo assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion.MethodsWe conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo.Measurements And Main ResultsCo-primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], -12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, -19%; 95% CI, -28 to -11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026).ConclusionsUse of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26).

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