SPAIN.

Methods	Study design: 26‐week randomised, open‐label, active control, parallel group study conducted in France, Lituania, Spain and UK between September 2006 and December 2007
Participants	654 adults aged 18 years or older. Inclusion Criteria: Age 18 years or over Minimum of 3 months history of asthma, diagnosed according to the American Thoracic Society (ATS) definition (9). Prescribed IGCS at a dose of at least 400 µg/day (320 µg/day released does) and within the approved label for the relevant drug during the last 3 months prior to Visit 1. Either daily maintenance treatment with both IGCS and LABA or daily treatment with IGCS alone (i.e. without LABA) A history of sub optimal asthma control the month prior to enrolment as judged by the investigator Use of at least 3 inhalations of as‐needed medication for symptom relief during the last 7 days before enrolment Exclusion Criteria: Previous treatment with Symbicort Single Inhaler; Use of any beta‐blocking agent, including eye‐drops and oral GCS as maintenance treatment. Known or suspected hypersensitivity to study therapy or excipients. A history of smoking less than 10 pack years. Asthma exacerbation requiring change in asthma treatment during the last 14 days prior to or at Visit 1.
Interventions	A comparison of Symbicort SiT 200/6 (Symbicort Turbuhaler delivered dose 160/4.5 µg, 1 inhalation b.i.d. plus as‐needed) and conventional best practice (according to GINA guidelines)
Outcomes	The primary outcome variable was time to first severe asthma exacerbations. The definition of a severe asthma exacerbation was oral corticosteroids for at least three days, ER treatment or hospitalisation for asthma. A secondary objective is to collect safety data for treatment in the two treatment groups in adult patients with persistent asthma
Notes	Results posted this trial (NCT 00385593) on clinicaltrials.gov in November 2010 (accessed December 2012). The AstraZeneca web report is inconsistent in describing the participants with SAE but confirmation of correct figures has been obtained from the sponsors..
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation list (confirmed by sponsors)
Allocation concealment (selection bias)	Low risk	"The investigator phoned to a free number of AstraZeneca randomisation centre. After checking that the patient met all selection and randomisation criteria, the investigator received the patient study number together with the assigned therapy. This was done consecutively from a centre specific randomisation listing, previously designed by AstraZeneca biometrical Unit All patients were rigorously assigned in a sequential manner, and always having previously checked that they met eligibility criteria." (Information provided by sponsors)
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐study design
Incomplete outcome data (attrition bias) All outcomes	High risk	58/328 (18%) on SiT did not complete the study, compared to 37/326 (11%) on conventional best practice
Selective reporting (reporting bias)	Low risk	Data have been obtained for all primary outcome measures