Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterised by progressive airflow limitation. It affects approximately 1 million people in the UK, is the fifth leading cause of death in the UK and costs the NHS approximately £1 billion annually.  Exacerbations of COPD account for 60% of NHS COPD costs and are associated with accelerated rate of lung function decline, reduced physical activity, reduced quality of life, increased mortality and increased risk of comorbidities such as acute myocardial infarction and stroke.   Current treatment includes inhaled corticosteroids, usually in combination with inhaled LABA to reduce exacerbation rates and improve lung function.  However the COPD airway inflammation is relatively insensitive to the anti-inflammatory effects of ICS and even high doses fail to prevent exacerbations.  It  has been observed that the reduced HDAC2 activity of COPD can be reversed in a dose-dependent manner by theophylline at ‘low’ concentrations.  

The TWICS trial, funded by the NIHR HTA programme, is a national, multi-centre randomised controlled trial which aims to determine the clinical effectiveness and cost-effectiveness of adding low dose theophylline (Uniphyllin MR 200mg od or bd [depending on smoking status and ideal body weight]) to inhaled corticosteroid therapy in patients with COPD and a history of exacerbations.  1424 participants will be recruited, half from primary care.  Patients will be randomised to low-dose theophylline or placebo for one year.  The primary clinical outcome is the number of participant reported COPD exacerbations necessitating a change in management (minimum change treatment with antibiotics and/or oral corticosteroids) during the one year treatment period.  

For more information please see the TWICS Study Website


Seonaidh Cotton; 




Trial protocol: