I currently lead pleural trials and trials methodology at the Oxford Respiratory Trials Unit (ORTU). My personal research area is clinical studies in malignant and infectious pleural disease, for which I received MRC Training Fellowship funding to conduct my D Phil. This involved:
- Completion of a phase IIb randomised controlled trial assessing novel intrapleural agents for efficient drainage in pleural infection (The Second Multi-centre Intrapleural Sepsis Trial (MIST2)). This trial involved the Medical Research Council CTU and the British Thoracic Society (11 centre UK double blind placebo controlled study). The study identified a novel enzyme combination treatment which improves radiological outcomes and was associated with reduced hospital stay (New England Journal of Medicine 2011)
- A single centre phase I toxicity study assessing a novel pro-inflammatory (TLR pathway) pleurodesis agent (Lipoteichoic Acid-T in Malignant Pleural Effusion trial), which identified a potential new strategy for pleurodesis in malignant pleural effusion (Lancet Oncology 2008)
- A Multicentre clinical trial addressing pragmatic questions in the treatment of malignant effusion (The First Therapeutic Intervention in Malignant Effusion Trial (TIME 1)) working with the MRC CTU. This study is a 2 x 2 factorial assessment of drain size and analgesia for malignant effusion pleurodesis, with projected completion of recruitment (n=320) in February 2011 and completion of follow up in June 2011.
- Two studies assessing the diagnostic value and interventional safety of thoracic ultrasound in pleural disease (Thorax 2008 and 2010)
- Novel diagnostic strategies to increase microbiological yield in pleural infection (prospective assessment of the use of blood culture bottles in the diagnosis of pleural infection, Thorax 2011).
Our current programme of research is focussed on practice changing pragmatic trials in specialised areas of respiratory medicine (pleural disease and sleep/ventilation). This includes:
- A prospective multinational cohort study of risk factors, microbiology and outcome in pleural infection (MRC grant)
- Prospective randomised assessment of the use of thoracic ultrasound in pleurodesis prediction for malignant effusion (funding decision awaited)
- Three randomised multi-centre studies assessing optimal analgesia and drain size, the clinical value of indwelling pleural catheters and intrapleural fibrinolytic agents in the treatment of malignant pleural effusion (the Therapeutic Intervention in Malignant Effusion (TIME) Trials (1/2/3)). These are at various stages of completion, with one study in the analysis phase currently
- The Pathogen Identification in Pneumonia and Pleural Infection (PIPAP) study, assessing molecular and novel radiological diagnostic techniques in thoracic infection
- A definitive phase III study assessing intrapleural tPA and DNase for the treatment of pleural infection (MIST3) - currently in planning / funding stage
- Detailed radiological description of pleural infection, and its correlates to microbiology and outcome
- Development work using a number of novel biological agents to manipulate pleural fluid production / pleurodesis.
Oxford Respiratory Trials Unit based studies in pleural disease and sleep medicine over the last 5 years have demonstrated the feasibility of multi-centre (>200 patient) recruitment in the UK into pragmatic trials of pleural disease and sleep, and have discovered novel treatment mechanisms in both pleural infection (MIST2) and malignant pleural effusion (LTAT phase I study). The infrastructure necessary to conduct multi-centre studies is now present, and extension in to other disease areas is now planned.
Key Highlights from the AABIP Evidence-Informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.
Miller CRJ. et al, (2020), Chest
Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments
Kanellakis NI. et al, (2020), Thorax, 75, 1004 - 1008
European Respiratory Society Statement on Thoracic Ultrasound.
Laursen CB. et al, (2020), The European respiratory journal
Association between Tunneled Pleural Catheter Use and Infection in Patients Immunosuppressed from Antineoplastic Therapy: A Multicenter Study.
Wilshire CL. et al, (2020), Annals of the American Thoracic Society
AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.
Miller RJ. et al, (2020), Journal of bronchology & interventional pulmonology, 27, 229 - 245