Malignant pleural effusions Cancer Pleural effusion, not elsewhere classified
Conditions
Interventions
Treatment (urokinase) arm: Intra-pleural urokinase (100,000 IU in 30 ml normal saline) administered 12 hourly for a total of 3 doses.
Placebo arm: Intra-pleural urokinase placebo (in 30 ml normal s
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Both males and females 2. A clinically confident diagnosis of pleural malignancy defined as: 2.1 Histocytologically proven pleural malignancy, or 2.2. Otherwise unexplained exudative pleural effusion in the context of histocytologically proven cancer elsewhere 2. A significant (>25% hemithorax area) multi-loculated or multi-septated pleural effusion (residual effusion on chest radiograph despite the presence of a patent in-situ chest tube) 3. Malignant pleural effusion requiring drainage and pleurodesis for symptom control 4. Written informed consent
Exclusion criteria
Exclusion criteria: 1. Age <18 years 2. Expected survival <28 days 3. Previous pneumonectomy on the side of the effusion 4. Positive ipsilateral pleural fluid gram stain or bacterial culture in the previous month 5. Previously received intra-pleural fibrinolytic agents into this effusion 6. Known sensitivity to urokinase 7. Coincidental stroke, major haemorrhage or major trauma 8. Major surgery in the previous 5 days 9. Chylothorax 10. Total blood white cell count <1.0 x 10^9 11. Patients who are pregnant or lactating 12. Irreversible bleeding diathesis or platelet count <100 x 10^9 13. Irreversible visual impairment 14. Inability to give informed consent or comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Breathlessness quantified from visual analogue scales. The primary outcome will be the change in mean daily visual analogue scale (VAS) score defining breathlessness over 28 days following randomisation. A daily VAS score will be obtained at a similar time each day to assess how breathless each patient has felt over the preceding 24 hours. The minimum clinically significant changes in the VAS scores have been established based on pilot data from previous studies determining the improvement in breathlessness associated with complete pleural fluid drainage with a permanent indwelling catheter. These are used in the power calculations. VAS methodology has been shown to be robust and reproducible. Patients who are known to be unable to record VAS scales (particularly the visually impaired) will be excluded (see Participants - exclusion criteria). Added 09/08/2016: 2. After adjuvant urokinase/placebo treatment, all patients will have a sterile 4 g talc slurry pleurodesis. Pleurodesis will be performed with talc graded to exclude majority of <10 µm particles to minimise toxicity. The hypothesis is that the urokinase treatment will improve pleural drainage such that subsequent pleurodesis is more effective. To assess whether adjuvant urokinase has improved the efficacy rate of pleurodesis, the failure rate of pleurodesis will be defined by the need for further pleural intervention within 28 days of randomisation. Recurrence of pleural fluid on imaging (e.g., chest radiograph or ultrasound) which is not causing sufficient breathlessness/pain to require further drainage will not be deemed pleurodesis failure. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Radiographic improvement in the area of the pleural effusion (measured as the difference in the proportion of the ipsilateral hemithorax occupied by the pleural effusion opacity on chest radiograph) on day three (the day of pleurodesis) 2. Total volume of pleural fluid drained 3. The proportion of patients requiring a further pleural fluid drainage to control breathlessness at 3 months 4. Self reported health status ('quality of life'), quantified from standard questionnaires at each trial assessment: Chronic Respiratory Disease Questionnaire (CRDQ) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30) 5. Health care costs (from health care utilisation and cost utility analysis from EQ-5D) | — |
Countries
United Kingdom
Outcome results
None listed