SD‐037‐0716.
| Methods | Study design: randomised, double‐blind, multi‐centre, parallel‐group Study duration: 12 months Number of study centres and location: 54 centres in 8 countries (Estonia, Germany, Latvia, Lithuania, Poland, Russia, the United Kingdom and Ukraine) Date of study: February 2001 to June 2002 |
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| Participants | N randomised (males): formoterol 333 (194), terbutaline 342 (208) Withdrawals: formoterol 23, terbutaline 28 Age, mean (range): formoterol 23 (6 to 73), terbutaline 24 (6 to 87) Asthma severity: intermittent Diagnostic criteria: ATS Baseline ICS use: not on ICS or LABA Baseline lung function, FEV1 mean [range] (% predicted): formoterol 3.11 L [0.98 to 5.56] (98%), terbutaline 3.15 L [1.14 to 6.80] (97%) Inclusion criteria: Visit 1. ≥ 6 years old with a diagnosis of asthma according to the ATS. Baseline FEV1 ≥ 80% predicted normal. Informed consent. Visit 2. Use of SABA on between 2 and 6 occasions during the last 2 weeks of the run‐in. Exclusion criteria: Visit 1. Use of ICS, other anti‐inflammatory treatment or LABA 3 months prior. Use of a beta‐blocker including eye drops. Respiratory infection affecting the asthma within 4 weeks prior to enrolment, as judged by the investigator. Smoking history ≥ 10 pack‐years. Use of unallowed medication. Women who were pregnant, breastfeeding or not using an acceptable method of contraception. Visit 2. < 16 morning PEF values in the diary, any significant respiratory infection, change in prescribed asthma medication during run‐in. |
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| Interventions | Run‐in: 3 weeks on Bricanyl terbutaline Turbuhaler 0.5 mg as‐needed. Single‐blind. Intervention: Oxis formoterol Turbuhaler 4.5 μg as‐needed Control: Bricanyl terbutaline Turbuhaler 0.5 mg Co‐medication: not ICS or LABA Definition of severe asthma exacerbation: the need for oral corticosteroid course or hospitalisation due to asthma |
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| Outcomes | Efficacy outcomes collected: primary variable: average morning PEF over the entire 12‐month period. Secondary variables: FEV1 pre‐ and post‐bronchodilator. Evening PEF, average daily number of inhalations of as‐needed, day‐ and night‐time asthma symptoms, time to first asthma exacerbation, provocative cumulative dose of metacholine giving a 20% fall in FEV1 (PD20). Safety outcomes collected: adverse events, clinical chemistry, haematology and urinalysis, ECG, systolic and diastolic blood pressure Time points: 1 screening visit, 1 at the end of run‐in and after 1, 2, 4, 6, 8, 10 and 12 months treatment. Subjects contacted by phone between visits to check adverse events and compliance. |
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| Funding | AstraZeneca | |
| Notes | Full text: Chuchalin A, Kasl M, Bengtsson T, Nihlen U, Rosenborg J. Formoterol used as needed in patients with intermittent or mild persistent asthma. Respiratory medicine 2005;99(4):461‐70 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "randomised" Subjects stratified according to age (6 to 11, 12 to 17, ≥18 years) and a different randomisation list was used fro each group |
| Allocation concealment (selection bias) | Low risk | From correspondence: "At visit one all subjects received an enrolment code. The subjects who fulfilled all inclusion and none of the exclusion criteria were given a subject number at visit two. Both the enrolment and subject numbers were allocated in consecutive order. If a subject discontinued participation in the study, this number was not to be re‐used." |
| Blinding (performance bias and detection bias) Objective outcomes; hospitalisation, deaths, SAEs | Low risk | From correspondence: "The study was double blind. All inhalers were identical in appearance" |
| Blinding (performance bias and detection bias) subjective outcomes; exacerbations requiring OCS, asthma‐related SAEs, withdrawal | Unclear risk | The drug safety department at AstraZeneca could break the treatment codes if an serious adverse events were suspected to be causally related to the study medications, if expedited reporting to authorities was required or in exceptional circumstances for other safety reasons |
| Incomplete outcome data (attrition bias) | Low risk | The results were analysed on an intention‐to‐treat basis |
| Selective reporting (reporting bias) | Low risk | None noted |
| Other bias | Low risk | None noted |