Eleanor K Mishra1, Amelia O Clive2, Genevieve H Wills3, Helen E Davies4, Andrew E Stanton5, Mohamed Al-Aloul6, Alan Hart-Thomas7, Justin Pepperell8, Matthew Evison6, Tarek Saba9, Richard Neil Harrison10, Anur Guhan11, Matthew E Callister12, Ramamurthy Sathyamurthy13, Sunita Rehal3, John P Corcoran14, Robert Hallifax14, Ioannis Psallidas14, Nicky Russell14, Rachel Shaw14, Melissa Dobson14, John M Wrightson14, Alex West15, Y C Gary Lee16, Andrew J Nunn3, Robert F Miller17, Nick A Maskell2, Najib M Rahman14,18. 1. 1 Norfolk and Norwich Pleural Unit, Norfolk and Norwich University Hospital NHS Foundation Trust, Norfolk, United Kingdom. 2. 2 Academic Respiratory Unit, School of Clinical Sciences, Southmead Hospital, University of Bristol, Bristol, United Kingdom. 3. 3 Medical Research Council Clinical Trials Unit and. 4. 4 Cardiff and Vale University Health Board, Cardiff, United Kingdom. 5. 5 Great Western Hospital, Swindon, United Kingdom. 6. 6 University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom. 7. 7 Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom. 8. 8 Somerset Lung Centre, Musgrove Park Hospital, Taunton, United Kingdom. 9. 9 Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, United Kingdom. 10. 10 North Tees and Hartlepool Hospitals NHS Foundation Trust, North Tees, United Kingdom. 11. 11 University Hospital Ayr, Ayr, United Kingdom. 12. 12 Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. 13. 13 James Cook University Hospital, South Tees, United Kingdom. 14. 14 Oxford Respiratory Trials Unit and Oxford Pleural Diseases Unit, Churchill Hospital, Oxford, United Kingdom. 15. 15 Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom. 16. 16 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; and. 17. 17 Research Department of Infection and Population Health, Institute of Epidemiology and Healthcare, University College London, London, United Kingdom. 18. 18 National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
Abstract
RATIONALE: Patients 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. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. METHODS: We 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 RESULTS: Co-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). CONCLUSIONS: Use 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).
RATIONALE: Patients 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. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. METHODS: We 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 RESULTS: Co-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). CONCLUSIONS: Use 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).
Authors: Rachelle Asciak; Rachel M Mercer; Robert J Hallifax; Maged Hassan; Eihab Bedawi; David McCracken; Nikolaos I Kanellakis; John M Wrightson; Ioannis Psallidas; Najib M Rahman Journal: ERJ Open Res Date: 2019-02-01
Authors: Lucía Ferreiro; Juan Suárez-Antelo; José Manuel Álvarez-Dobaño; María E Toubes; Vanessa Riveiro; Luis Valdés Journal: Can Respir J Date: 2020-09-23 Impact factor: 2.409