Asthma Clinical Research Network (ACRN)

Measuring Inhaled Corticosteroid Efficacy (MICE)

NULL HYPOTHESIS

There is no variability in the efficacy/systemic effect relationships for the various measures of efficacy (pulmonary function, bronchial hyperresponsiveness and asthma control), using inhaled corticosteroids BDP (Vanceril Double Strength, 84 µg per inhalation) and FP (Flovent-44, 44 µg per inhalation), when they are administered with the Opti-Chamber spacer in doses resulting in minimal cortisol suppression (<5%), 20-30% cortisol suppression and 40-60% cortisol suppression.

DESIGN

The MICE trial was a 24-week, randomized, open-label, prospective multicenter trial examining the effect of inhaled BDP and FP administered via Opti-Chamber on different outcomes in subjects with persistent asthma. After a 2-week run-in period, during which the subjects received placebo inhaler and as-needed albuterol to reinforce training and compliance, subjects were randomized to BDP or FP.  Each patient underwent three 6-week periods with increasing doses of their respective ICS.  The doses for BDP were 168 µg per day, 672 µg per day, and 1344 µg per day. The corresponding doses of FP were 88 µg per day, 352 µg per day, and 704 µg per day.  Following the 18 weeks of ICS administration, the subjects discontinued the study dose of inhaled BDP or FP with Opti-Chamber and were administered Flovent Diskhaler 250, 4 inhalations twice daily (2000 µg per day) for a 21-day period.  The efficacy outcomes included FEV₁, post-bronchodilator maximum FEV₁, change in PC₂₀ based on methacholine-induced bronchospasm, and inhibition of exercise-induced bronchospasm.  Additional outcomes included resolution of inflammation based on changes in sputum cytology, rate of improvement in FEV₁ over time, changes in exhaled nitric oxide, symptom-free days, and changes in asthma control as assessed by the asthma control questionnaire.

RESULTS

Enrollment for the MICE trial began in May 1999 and the last patient visits occurred in April 2000.  Fifteen patients were randomized to each ICS group.  Near-maximal FEV₁ and PC₂₀ effects occurred with low-medium dose for each ICS.  High-dose ICS therapy did not significantly increase efficacy, but it did significantly incease the systemic effect.  Significant inter-subject variability was observed within both ICS groups.  It is possible that higher doses are necessary to manage more severe patients or to achieve goals of therapy not evaluated in the MICE trial.  The major publication appeared in JACI: