Award Title: Randomised Thoracoscopic Talc Poudrage + Indwelling Pleural Catheters versus Thoracoscopic Talc Poudrage only in Malignant Pleural Effusion (R-TACTIC)
Funder: Department of Health and Social Care

Abstract: Research Question  Does the novel combination of Thoracoscopic Talc Pleurodesis (TTP) + Indwelling Pleural Catheter (IPC) result in reduced total time in hospital and reduced breathlessness over 1 month post randomisation compared with standard care (TTP alone) in Malignant Pleural Effusion (MPE)?     Background  MPE, where large volumes of fluid gather in the lining of the lung due to metastases to the pleura, is common and increasing (50,000 new cases / year) in the UK(1-4). MPE causes disabling breathlessness and distress.     Standard Treatment involves drainage of the fluid through tubes inserted between the ribs to relieve symptoms, but fluid recurs in >90% without further treatment(5). Definitive treatment to prevent recurrence is achieved via a camera inserted in the pleural space under sedation (thoracoscopy)(6, 7), when biopsies can be taken to establish diagnosis, and a chemical (talc) is inserted to fuse the lung to the chest wall (thoracoscopic talc pleurodesis, TTP) (8). This requires admission for 3-5 days and prevents fluid long-term in only 60%(5).     IPCs are used later in treatment when TTP fails(5). These are tubes inserted as day cases(9) and allow patients to drain at home using vacuum bottles. They provide symptom control(10-12), improve quality of life (13-15), allow long-term drainage and have no “failure” rate.     Novel Treatment: Combining TTP + IPC early in care as the first definitive procedure would allow patients to be diagnosed, treated and sent home in one day after a single procedure, drain fluid at home and achieve pleurodesis without any hospital stay. In observational studies, 80% of TTP+IPC treated patients have IPCs removed at 2 weeks (16).     Aims / Objectives  To assess the effect of combined TTP + IPC early in care through a randomised comparison with the standard pathway. To use qualitative methods to understand the impact of the two treatments on patients and carers.     Methods  1. A Definitive Randomised Controlled Trial conducted in 142 MPE patients in centres with a track record of delivery to MPE studies (n>1000).     Patients randomised to:    Standard care (TTP)  Intervention (TTP+IPC in a combined procedure)      Co-Primary outcomes:    Time in hospital over 1 month post randomisation.  Mean breathlessness over 1 month post randomisation using 100mm VASd score which is validated in MPE(17), MCID is established and is reliably measured (18, 19).      2. Qualitative Study Semi-structured interviews with up to 24 patient/care diads (patient and carer interviewed together)  (10-12 diads per treatment arm), to understand impact of treatment at 3 months.     Timelines for delivery    Ethics, regulatory approval, database, CRF (3 months)  Centre setup (3 months)  Recruitment (142 patients, 24 months recruitment).  Follow up (3 months).  Database lock, analysis, publication (3 months).  Total 36 months.      Anticipated Impact / Dissemination  If TTP+IPC is effective, the results will change UK practice for thousands of patients, reduce hospital stay and healthcare costs, improve quality of life and prevent further pleural procedures. We will disseminate results widely through patient and specialist meetings and publications, so that results impact care immediately.

Lay Abstract: The purpose of this study is to improve treatment of patients with malignant pleural effusions (MPE).     MPE occurs when cancer spreads to the space around the lung (the pleural space) where fluid accumulates. Any cancer (lung, breast, ovarian, bowel) can cause this, and fluid causes breathlessness with a major impact on quality of life, causing distress for patients and families.     To help patients, we drain fluid to relieve breathlessness. The fluid usually comes back and so a further "sticking" procedure is needed. This involves draining fluid and inserting a chemical to fuse the cavity, done using a keyhole procedure under sedation (thoracoscopic talc pleurodesis, TTP) when biopsies can also be taken. This requires admission to hospital for 3-7 days, and fails (the fluid comes back) in 40% of cases.     When pleurodesis fails, we insert a small tube in the chest which the patient is sent home with, called an indwelling pleural catheter (IPC). Patients drain fluid themselves at home. Previous studies show IPCs are well tolerated and improve symptoms, and fluid can be drained long-term. However, patients experience pain, there is a risk of infection, and drainage at home is inconvenient.     Combining treatments at the start (TTP + IPC) might achieve the “best of both worlds”. This would provide diagnosis and treatment for MPE in a single procedure, avoid admission completely and prevent “failure”, leading to better symptom control and quality of life. Patients with MPE have told us that avoiding time in hospital and improving breathlessness are their top priorities.     We will assess this through a randomised trial in five centres, comparing TTP + IPC with standard care (TTP). We will measure time spent in hospital, symptoms including breathlessness, costs and impact on carers and patients to establish which treatment is best. We will conduct this study in 5 expert centres which have previously conducted many randomised trials in MPE patients, and have shown they can perform such studies effectively and safely.     A survey of patients with MPE identified being at home as a priority, and the primary focus of this study is time in hospital. We will disseminate results widely including through patient and specialist meetings and publications, so that results impact care immediately.

Research Activity Codes: 6.3 MEDICAL DEVICES
Health Categories: CANCER AND NEOPLASMS