The Calverley study design
This study by Calverley and colleagues [1] was a 1-year, international, randomised, double-blind, placebo-controlled prospective study designed to test whether the short-term improvement in COPD that follows a period of treatment optimisation with oral prednisolone and inhaled formoterol could be maintained over a longer time by treatment with Symbicort®, budesonide, formoterol or placebo.
The study involved 1022 patients with moderate to severe COPD (pre-bronchodilator forced expiratory volume in 1 second [FEV1] < 50% predicted normal). During run in, treatment was intensified with a 2-week course of formoterol and oral corticosteroids. Patients were then randomised to maintenance treatment with two inhalations twice daily of Symbicort (160/4.5 μg), comparable doses of either budesonide or formoterol, or placebo. All patients used terbutaline as needed for symptom relief. The primary efficacy variables were time to first exacerbation and change in post-medication FEV1.
The Calverley study results
This study showed that Symbicort maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either monotherapy alone or placebo.
- Symbicort significantly prolonged time to first severe exacerbation by 100, 76 and 158 days compared with formoterol, budesonide and placebo, respectively (all P < 0.05).
- Symbicort reduced the risk of an exacerbation by 23%, 30% and 29% compared with budesonide, formoterol and placebo, respectively.
- Symbicort maintained the improvement achieved in FEV1 and morning peak expiratory flow during run throughout the study. These measures declined rapidly from the end of run in and remained low until the end of study with all other treatments and placebo.
- At study entry, patients had poor St Georges Respiratory Questionnaire (SGRQ) scores, indicating poor health-related quality of life. At end of run in, total scores had improved by a clinically important mean of 4.5 points. Symbicort sustained further improvement in the SGRQ score and at the end of the 1-year study, the mean improvement from baseline versus placebo was 7.5 points (P < 0.001), 3.0 points versus budesonide (P < 0.05) and 4.1 points versus formoterol (P < 0.01).
- All treatments were well tolerated and had similar adverse event profiles.
Calverley study: Improvement in health related quality of life [1]
References
- Calverley PM, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic pulmonary disease. Eur Respir J 2003; 22:912–919.
