Randomisation Following informed consent, patients will be randomly assigned in a 1:1 ratio using minimisation with a random element to undergo either chest drain insertion with talc slurry pleurodesis or thoracoscopy with talc poudrage. The day of randomisation is defined as day 0. Although the allocated trial Tofacitinib buy procedure may be performed within 3 days of randomisation, every effort should be made to perform the procedure

immediately afterwards. Treatment allocation will be performed over the telephone by the ORTU. The randomisation sequence will be generated using a validated, online randomisation service (Sealed Envelope, London, UK; http://www.sealedenvelope.com). The minimisation factors are: Type of underlying malignant disease (mesothelioma, lung cancer, breast cancer, other); WHO/Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1; 2 or 3). Patients and clinicians will not be blinded to treatment allocation. Standard care All patients should have been discussed in their local or regional tumour-specific MDT. For all issues other than those pertaining to the drainage and management of the MPE, treatment discretion lies with the primary clinician. Normal clinical review during the trial period will take place in the usual outpatient or inpatient setting, and will typically be carried out by oncologists or respiratory physicians. The frequency of clinical review will depend on patient choice, severity of symptoms

and clinical

discretion. In general, patients who are managed with chemotherapy for underlying malignancy are typically reviewed every 2–3 months. Patients can withdraw from the trial at any time without their clinical care being affected. Co-enrolment in other clinical trials will be discussed on an individual patient basis, but patients should not be co-enrolled into any trial which specifically aims to directly influence pleural fluid production or drainage. Interventions The full trial specific procedures (TSP) for the two treatment arms can be found in online supplementary appendices 4 and 6. Control (talc slurry) arm Patients will have a small-bore (<14 Fr) chest drain inserted under aseptic conditions using the Seldinger technique, with appropriate local Cilengitide anaesthesia and premedication as necessary. A suitable site for drain placement will be identified using contemporaneous ultrasound. Drains will only be inserted by persons with adequate training and experience. Trial pleural fluid samples (see section below) should also be taken as necessary. A CXR should be performed between 18 and 24 h after drain insertion. If there is no evidence of trapped lung or significant fluid, as determined by the patient’s primary physician, then the patient should have 4 g talc slurry instilled through the chest drain, following the appropriate TSP. Patients who continue to have evidence of significant pleural opacification may need to undergo further imaging to confirm the cause.