The clinical and cost-effectiveness of temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations; a pragmatic, randomised, normal care-controlled, clinical trial

DESIGN Pragmatic, multi-centre, open label, randomised, normal care-controlled, clinical trial with two parallel treatment arms of equal size. Participants will be randomised to one of two self-management plans using a computer-based randomisation system (Nottingham Clinical Trials Unit) stratified by centre, smoking status, and maintenance inhaled corticosteroid dose. Participants will follow the plan for 12 months from randomisation. This approach is similar to that of our previously published studies showing that a two-fold increase is not effective (Lancet 2004) but a four-fold increase may be effective (AJRCCM 2009) and is therefore tried and tested. SETTING General practice and hospital outpatient NHS care settings. TARGET POPULATION Participants will be recruited from across England via five Primary Care Research Networks to capture a wide and representative sample population, reflective of the mix of people treated with asthma in the NHS. Selection criteria are as inclusive as possible to ensure generalisability whilst ensuring adequate outcome events. Participants must be 18 years or older, have a documented clinical diagnosis of asthma, be taking an inhaled steroid (between 400 and 2000 mcg beclomethasone diproprionate or equivalent) and have suffered at least one exacerbation requiring systemic corticosteroids in the previous 12 months (because these patients are more likely to suffer a further exacerbation). Exclusion criteria include, treatment with maintenance oral steroids or patients using budesonide formoterol combination inhaler for both maintenance and relief (SMART approach) and patients with a clinical diagnosis more suggestive of smoking induced COPD (based on smoking history > 20 pack years and lack of reversibility). HEALTH TECHNOLOGY The patient self-management plan is central to the asthma care pathway. Involvement of Asthma UK allows us to use a modified version of the Asthma UK self management plan (attached pdf file), ensuring continuation of normal care for the control group. The plan advises patients on how to take their treatment when they are well - zone 1, what to do when their asthma control starts to deteriorate - zone 2 and what to do if their asthma continues to deteriorate - zone 3 and 4. The study self-management plan will include instructions to take a four-fold increase in inhaled steroid dose OR to use bronchodilator therapy for symptoms (current recommendation in international guidelines) at zone 2 . Once started, the additional treatment will be continued until symptoms and peak flow have returned to baseline or for a maximum of 14 days. All participants will be contacted monthly by an automated text service as a reminder to contact their local centre when their symptoms and peak flow trigger the zone 2 criteria. Approximately 21 days after this contact a study visit will be arranged to collect the outcome data. All participants will, therefore, be treated in exactly the same way except for the type of intervention recommended at step 2 of their self-management plan. We have selected 2000 mcg beclomethasone diproprionate or equivalent as the upper entry dose because this ensures inclusion of the great majority of patients treated in primary and secondary care. To minimise the risk of systemic adverse effects we have limited the treatment period at the higher dose to 14 days but in our previous study most patients needed the higher dose for approximately 7 days.