Table 3.

Notable Trials Investigating Single Maintenance and Reliever Therapy (SMART) for Asthma

Patel et al.4Bisgaard et al.16
Study design12-month, open-label RCT12-month, double-blind RCT
PopulationAdults 16 to 65 years old with:

  • Asthma requiring daily ICS for maintenance, and

  • An asthma exacerbation requiring healthcare presentation and oral corticosteroids or nebulized bronchodilator in the preceding year

Children 4 to 11 years old with

  • Asthma history ≥6 months, and

  • At least one clinically important asthma exacerbation in the past 12 months

SMART componentsBudesonide-formoterol (200/6 µg per actuation) 2 actuations twice daily plus 1 actuation as needed for symptom reliefBudesonide-formoterol 80/4.5 µg daily plus additional doses for symptom relief
Comparator(s)Budesonide-formoterol (200/6 µg per actuation) 2 actuations twice daily plus 1 to 2 actuations of salbutamol (100 µg per actuation) as needed for symptom reliefFixed combination:
Budesonide/formoterol 80/4.5 µg daily plus terbutaline 0.4 mg for symptom relief
Fixed-dose budesonide:
Budesonide 320 µg daily plus terbutaline 0.4 mg for symptom relief
Primary outcomeProportion of patients with at least one high-use episode of β agonist*
56% versus 45%
RR 1.24; 95% CI, 0.99-1.56; P = .058		Time to first exacerbation
P < .001 compared to fixed combination
P = .02 compared to fixed-dose budesonide
Other notable reported clinical outcome(s)Mean (S.D.) days of high use
5.1 (14.3) versus 8.9 (20.9)
Relative rate 0.58; 95% CI, 0.39-0.88; P < .01
Number of days with zero actuations of maintenance budesonide-formoterol
23.9 (32.6) versus 33.6 (42.8)
RR 0.72; 95% CI, 0.55-0.95; P < .022		Overall exacerbations
Fixed combination:
14% versus 38%
HR 0.34; 95% CI, 0.19-0.60, P < .001; NNT = 5
Fixed-dose budesonide:
14% versus 26%
HR 0.49; 95% CI, 0.27-0.90, P < .022; NNT = 9
At least 1 severe exacerbation
19% versus 33%
RR 0.56; 95% CI, 0.38-0.84; P < .004; NNT = 8
Number of courses of oral corticosteroids per year of follow up
0.80 (2.5) versus 1.1 (1.9)
Relative rate 0.58; 95% CI, 0.41-0.84; P < .004		Exacerbations requiring medical intervention
Fixed combination:
0.08/patient versus 0.40/patient, P < .001
Fixed-dose budesonide:
0.08/patient versus 0.28/patient, P < .001

  • ↵*>12 actuations of budesonide-formoterol per day in SMART group and >16 actuations per day of salbutamol in comparator group.

  • Abbreviations: SD, standard deviation; CI, confidence interval; RCT, randomized controlled trial.