Najib M Rahman

Overview

I direct the Oxford Respiratory Trials Unit (ORTU), and lead trials methodology and the Pleural Disease Group. ORTU has a track record in design, delivery and analysis of trials in a number of areas of Respiratory Medicine including pleural disease, sleep apnoea, airways disease, cancer, radiology and physiological.

My group conducts a diverse portfolio of research in pleural infection, undiagnosed pleural effusion, malignant pleural effusion, mesothelioma, pneumothorax, imaging and intervention. This work spans laboratory based translational work, early phase discovery science and practice changing clinical trials at oligo and multi-centre levels.

Previous work in my group has included work in the following areas:

Pleural Infection:

• The MIST2 trial (The Second Multi-centre Intrapleural Sepsis Trial)- a double blind placebo controlled trial which identifed a novel enzyme combination treatment which improves outcomes  (Rahman et al, NEJM 2011). This treatment has become standard practice across the world.
• Derivation and  validation of a risk score in pleural infection which  predicts 3 month mortality (RAPID, Rahman et al, Chest 2014)
• PILOT (The Pleural Infection Long Term Outcome Study) – prospective 550 patients study from 25 centres (international) which has established a biobank of fluid / blood and validated the RAPID score (Corcoran et al, ERJ 2020).
• AUDIO – pilot feasibility study demonstrating increased diagnostic yield using image guided pleural biopsy (Psallidas et al, Chest 2018)

Malignant Pleural Effusion

• A single centre phase I toxicity study assessing a novel pro-inflammatory (TLR pathway) pleurodesis agent, identifying a novel pleurodesis stragey (Rahman et al, Lancet Oncology 2008)
• TIME1 (The First Therapeutic Intervention in Malignant Effusion Trial): A multicentre 2 x 2 factorial randomised controlled trial (n=320), defining optimal drain size and analgesia for pleurodesis (Rahman et al, JAMA 2015)
• TIME2: multicentre randomised trial (n=120), established the role of indwelling pleural catheters (IPCs) in  treatment (Davies et al, JAMA 2012).
• TIME3: multicentre placebo controlled trial assessing intrapleural fibrinolysis in septated malignant effusion (Mishra et al, AJRCCM 2018).
• TAPPS: multicentre controlled trial comparing thoracoscopic poudrage pleurodesis to slurry pleurodesis (n=330) in collaboration with the Bristol Pleural Unit (Bhatnagar et al, JAMA 2019)
• IPC-Plus: multicentre controlled trial demonstrating  utility of pleurodesis via IPC in collaboration with the Bristol Pleural Unit (Bhatnagar et al, New England Journal of Medicine 2018)
• Translational studies validating a biological risk score (Psallidas et al, Lancet Oncology 2018) and deriving in vitro malignant cell lines from patient pleural fluid (Kanellakis et al, Thorax 2020).

Pneumothorax

• The largest UK primary spontaneous pneumothorax (PSP) treatment trial to date (n=240, 25 UK centres) demonstrating safety and utility of ambulatory management (Hallifax et al, Lancet 2020)
• The world’s largest study on the epidemiology of pneumothorax (n=170,000) (Hallifax et al, JAMA 2019)
• Investigation of predictive parameters in PSP using digital measurement (Hallifax et al, Thorax 2019)

Ongoing research

ORTU is currently delivering over 50 studies, including academically led and industry sponsored research. Specific to pleural disease, our current programme of work includes practice changing pragmatic trials in pleural disease, while creating increased focus on translational work to identify underlying mechanisms and phenotypes. This includes:

• Investigation of biological mechanisms in pleural infection; mechanisms of action of intrapleural fibrinolytic using human samples (Kanellakis et al, BMJORR 2019), molecular microbiology and inhibitors of fibrinolysis and treatment response  (Komissarov et al, Am J Physiol Lung Cell Mol Physiol 2016)
• MIST3 - Randomised controlled trial comparing early video assistant thoracoscopic surgery to intrapleural fibrinolytic (feasibility)
• Early phase study to assess contrast enhanced  ultrasound in septated effusion
• Ongoing pragmatic trials in malignant pleural effusion management, including use of bedside thoracic ultrasound to predict outcome  (SIMPLE, Marie Curie / CRUK funded, n=330), and  assessment of combined intervention (IPC + poudrage, NIHR funded).
• Prospective large scale pragmatic assessment of complications from pleural procedures (PROSPECT).
• Translational studies addressing  mechanism and aetiology of air leak in pneumothorax (PREFECT).
• Randomised assessment of early use of digital suction too enhance the PSP care pathway.
• Acceleration of the Undiagnosed pleural effusion pathway using early image guided biopsy and indwelling pleural catheters.