Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma
- D B Price1,
- D Hernandez2,
- P Magyar3,
- J Fiterman4,
- K M Beeh5,
- I G James6,
- S Konstantopoulos7,
- R Rojas8,
- J A van Noord9,
- M Pons10,
- L Gilles11,
- J A Leff11,
- for the Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group*
- 1University of Aberdeen, Aberdeen, UK
- 2Hospital Civil de Guadalajara, Guadalajara, Mexico
- 3Department of Pulmonology, Semmelweis University, Budapest, Hungary
- 4Pucrs Medical School, Porto Alegre, Brazil
- 5Pulmonary Division, University Hospital, Mainz, Germany
- 6Spring House Surgery, Bolton, Lancashire, UK
- 7Pneumonology Clinic, Medical School University Hospital of Ioannina, Greece
- 8Tucuman National University, San Miguel de Tucumán, Argentina
- 9Atrium Medical Center, Department of Pulmonology Heerlen, The Netherlands
- 10Ospedale Civico, Lugano, Switzerland
- 11Merck and Co Inc, Whitehouse Station, New Jersey, USA
- Correspondence to:
Professor D B Price, Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre, Westburn Road, Aberdeen AB25 2AY, UK;
- Accepted 18 November 2002
- Revised 21 October 2002
Background: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma.
Methods: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 μg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 μg/day (n=448) or budesonide 1600 μg/day (n=441) for 12 weeks.
Results: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1–3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to “as needed” β agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated.
Conclusion: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.
David Price and Jon Leff undertook the initial study design, protocol production, co-led the evaluation, co-wrote the data analysis plan, reviewed the statistics report and prepared the manuscript for publication. Leen Gilles contributed to the study design, co-wrote the data analysis plan, undertook the statistical analysis and contributed to the manuscript. All other authors reviewed and contributed to study design, protocol review, patient recruitment, data analysis review and input into the manuscript. David Price, Leen Gilles and Jon Leff are guarantors for the paper.
Conflicts of interest: David Price either through his role at the University of Aberdeen or personally has received grants, honoraria or educational support from the UK NHS R&D programme, 3M Pharmaceuticals, Abbot Laboratories, Altana, AstraZeneca, GlaxoSmithKline, Ivax, Merck, Sharpe and Dohme, Novartis, Schering Plough and Trinity Pharmaceuticals. He does not possess any pharmaceutical shares.
↵* A complete list of members of the COMPACT International Study Group is provided in the Appendix.