Oxford Respiratory Trials Unit (ORTU)
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The UKCRN Oxford Respiratory Trials Unit (ORTU) is a specialist centre for the administration and recruitment of patients to respiratory trials based at the Churchill Hospital in Oxford.
The UKCRN Oxford Respiratory Trials Unit (ORTU) is a specialist centre for the administration and recruitment of patients to respiratory trials. We are based at the Churchill Hospital in Oxford. The ORTU is one of few UKCRN (UK Clinical Research Network) registered Clinical Trials Units specialising in respiratory research. We run many of our projects in partnership with the MRC Clinical Trials Unit (MRC CTU) and as part of the Comprehensive Local Research Network (CLRN) portfolio. We run both national and international trials related to our own work, as well as supporting trials led by other teams.
The work within the ORTU is funded by various agencies including the Human Tissues Authority, UK Medical Research Council, British Lung Foundation, National Cancer Research Institute and British Heart Foundation. We also coordinate the Respiratory Specialty Interest Group of the Thames Valley Comprehensive Local Research Network.
The ORTU has a special interest in both pleural malignancy and pleural infection. About 300,000 patients need treatment for malignant pleural effusion per year in the UK and USA. These patients suffer breathlessness and decreased quality of life. Improving these symptoms is the major focus of our work within this area. Pleural infection is becoming increasingly common and greater than 30% of these patients either die or need surgery to treat their infection. We are currently recruiting to three clinical trials in patients with malignant pleural disease, the TIME trials (Trials In Malignant Effusions):
- TIME1: a 2 by 2 factorial trial studying the effects of chest drain size and analgesia (opiates versus non-steroid anti-inflammatory drugs) on pain and pleurodesis efficacy following chest drain insertion.
- TIME2: a randomised trial comparing standard treatment with indwelling pleural catheters as first line treatment for malignant pleural effusions.
- TIME3: a trial looking at the effects of intrapleural fibrinolytics on relief of breathlessness and pleurodesis success for patients with septated malignant effusions.
We are also coordinating a second trial in pleural infection, MIST2 (Multicentre Intrapleural Sepsis Trial).
Previously, we have completed other trials in malignant pleural disease that include studies to define the safest preparation and grade of talc used to treat malignant pleural effusions. This work was one of the datasets that led to the UK Medicines and Healthcare products Regulatory Agency changing its regulation requirements for talc for medical use within the UK.
We have also completed a randomised trial that compared the diagnostic accuracy of biopsy methods for pleural malignancy from 47% to 87%, reducing the need for diagnostic pleural biopsies and further invasive tests within the UK.
In the area of pleural infection, we have defined the modern bacteriology of this disease, improving antibiotic choices for these patients.
The current work of the sleep unit centres on the cardiovascular complications of Obstructive Sleep Apnoea (OSA). OSA is a common respiratory problem affecting 2-4% and 1-2% of middle aged males and females respectively. Mild disease has a prevalence of up to 24%. The association between OSA and cardiovascular disease is not fully understood. Apnoeas are associated with large swings in intra-thoracic pressure, hypoxaemia, reflex sympathetic activation and a transient increase in blood pressure (sometimes exceeding 200mmHg); blood pressure is also raised whilst awake and asleep. Rises in blood pressure induce shear stresses in blood vessel walls (this is thought to cause vascular wall damage and atheroma formation in other settings).
The MOSAIC (Multi-centre Obstructive Sleep Apnoea Interventional Cardiovascular) trial is looking at the effect that continuous positive airway pressure (CPAP) therapy has on cardiovascular risk in patients with mild-moderate obstructive sleep apnoea.
The recent NICE Technology Appraisal of the use of continuous positive airway pressure (CPAP) in obstructive sleep apnoea hypopnoea syndrome (OSAHS) concluded that CPAP was an effective and cost efficient treatment for OSAHS in middle-aged people. However it identified evidence gaps with a need for trials in less symptomatic patients in older patient groups. A new randomised controlled trial, PREDICT (Positive airway pressure in older patients: a randomised controlled trial) aims to provide evidence regarding CPAP efficacy for OSAHS in older people. Since CPAP is the treatment of choice for OSAHS, the results of this trial will directly inform clinical practice and health care planning at both national and international levels.
More recently we have expanded the search for OSA and adverse vascular interactions. We demonstrated a high prevalence of OSA in diabetes and also showed an association between OSA and diabetic retinopathy. Currently we are conducting a proof of principle study to assess whether treating patients with CPAP therapy who have both OSA and diabetic macular oedema improves their retinal health, therefore, possibly offering an alternative to laser therapy.
Work carried out by Kohler et al in Oxford has already shown an association between OSA and thoracic aneurysm expansion and we are currently extending this hypothesis by screening individuals with aortic aneurysms for OSA. We are also identifying whether there is an association between the rate of expansion and presence of OSA.
Jenkinson et al performed some of the first studies looking at patient experience and quality of life when using CPAP and showed that SF-36 revealed substantial adverse effects on subjective health in those with OSA, and that NCPAP treatment produced dramatic positive effects. This work was one of the datasets that informed the NICE appraisal mentioned above.
Previous major completed projects in OSA have included an RCT showing that CPAP reduces BP in severe OSA sufficient to reduce stroke risk by approximately 25%
Stradling and Crosby et al identified 1001 men of which 900 agreed to be visited at home for assessment of snoring, daytime sleepiness and overnight oximetry. It is this work that formed the foundation of our understanding about the prevalence of Sleep apnoea in the general population. They also identified that OSA correlated best with upper body obesity as opposed to general obesity.
Early work conducted by the Sleep unit (Nicoll et al) looked at a new physiological signal, the pulse transit time (PTT), which is an indirect measure of blood pressure changes. They concluded that PTT was a non-invasive, objective measure of inspiratory effort and respiratory arousals. The PTT compares favourably with other measures of disease severity and shows improvement with treatment. This signal is now incorporated in several commercial sleep study systems.
The ORTU and the Sleep Unit is also involved in a multi centre trial to look at the possible benefits of long term overnight non-invasive ventilation (NIV) in patients with COPD and chronic CO2 retention. This is an RCT comparing NIV with usual best therapy including long term oxygen.