Research

Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

Björn Ställberg¹ , Olof Selroos² , Claus Vogelmeier³ , Eva Andersson⁴ , Tommy Ekström⁴ and Kjell Larsson⁵

¹  Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, Uppsala University, Sweden

²  Semeco, Ängelholm, Sweden

³  Universitätsklinikum Giessen and Marburg, Marburg, Germany

⁴  AstraZeneca, Södertälje, Sweden

⁵  Lung and Allergy Research Unit, Karolinska Institutet, Solna, Sweden

author email corresponding author email

Respiratory Research 2009, 10:11doi:10.1186/1465-9921-10-11

Published:	19 February 2009

Abstract

Background

Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation.

Methods

This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV₁ 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home.

A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV₁ 45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV₁ was the primary efficacy variable. Non-inferiority was predefined.

Results

Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV₁-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified.

Conclusion

High dose budesonide/formoterol was as effective as prednisolone plus formoterol for the ambulatory treatment of acute exacerbations in non-hospitalized COPD patients. An early increase in budesonide/formoterol dose may therefore be tried before oral corticosteroids are used.

Clinical trial registration

NCT00259779