FACET

Incomplete

Pauwels RA, et al. "Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group". The New England Journal of Medicine. 1997. 337(20):1405-1411.
PubMed

Clinical Question

In patients with asthma, does the addition of formoterol to budesonide decrease asthma exacerbation rates?

Bottom Line

The addition of formoterol to budesonide decreased asthma exacerbation rates, improved lung function, and decreased asthma symptoms. Patients in the high dose budesonide group in addition to formoterol had the greatest reduction in asthma exacerbation rates.

Design

• Multicenter, double-blind, parallel-group, randomized, controlled trial
• N= 852
  • Lower-dose Budesonide + Placebo (n=213)
  • Lower-dose Budesonide + Formoterol (n=210)
  • Higher-dose Budesonide + Placebo (n=214)
  • Higher-dose Budesonide + Formoterol (n=215)
• Setting: 71 centers in nine countries (Belgium, Canada, The Netherlands, Israel, Italy, Luxembourg, Norway, Spain, and the United Kingdom)
• Enrolment: April 1994 to April 1995
• Mean follow-up: 12 months
• Analysis: Intention-to-treat
• Primary outcome: The rates of severe and mild exacerbations of asthma

Population

Inclusion Criteria

• Asthma for at least 6 months
• Treatment with ICS for at least 3 months
• Age 18-70
• Baseline FEV1 at least 50% predicted with 15% increase after administration of 1 mg of terbutaline

Exclusion Criteria

• Daily use of more than 2000 mcg of beclomethasone, 1600 mcg of budesonide via MDI, 800 mcg of budesonide via Turbuhaler, or 800 mcg of fluticasone
• Three or more courses of oral steroids in the past 6 months
• Hospitalized for asthma in the past 6 months

Baseline Characteristics

• Mean age: 42 years
• Daytime symptom score: 0.51
• Nighttime symptom score: 0.28
• FEV1: 2.47 L
• PEF: 393 L/min

Interventions

• Four week run in period with budesonide 800 mcg inhaled twice daily + PRN terbutaline 250mcg
• After run in period, participants were randomized to one of four groups if they had stable asthma:
  • Low dose budesonide (total daily dose 200 mcg) + placebo
  • Low dose budesonide (total daily dose: 200 mcg) + formoterol (total daily dose: 24 mcg)
  • High dose budesonide (total daily dose: 800 mcg) + placebo
  • High dose budesonide (total daily dose: 800 mcg)+ formoterol (total daily dose: 24 mcg)
• All participants were given terbutalin to use as a rescue medication
• Scheduled visits occurred with all participants:
  • At the start of the run-in period
  • At the start of treatment
  • At 1, 2, 3, 6, 9 and 12 months of treatment

Outcomes

Comparisons are 1. fometerol vs. placebo and 2. lower dose vs. higher dose budesonide.

Primary Outcomes

Rates of mild exacerbations of asthma per patient per year

1. 21.3% vs. 35.4%

2. 13.4% vs. 22.3%

Rates of severe exacerbations of asthma per patient per year

1. 0.67% vs. 0.91%

2.

Secondary Outcomes

Diary card data

Clinic visits

Episode-free days