Objectives

The CARE-PACT study was designed to determine whether, in children with mild to moderate persistent asthma, similar or greater asthma control could be obtained with a regimen of a LABA and half the dose of an ICS known to be effective compared to an ICS alone or a LTRA.

Background

Although children with mild to moderate persistent asthma benefit from daily maintenance medication to prevent symptoms and exacerbations, the regimen with the best benefit/risk ratio has not yet been defined. While an inhaled corticosteroid (ICS) is effective in controlling childhood asthma, an ICS is associated with mild reduction in growth velocity. A leukotriene receptor antagonist (LTRA) is an alternative to an ICS, but evidence suggests an ICS provides better asthma control. Another alternative is to add a long-acting β-agonist (LABA) to an ICS to allow reduction in the ICS dose, however, this has not been well studied in children. The Childhood Asthma Research and Education (CARE) Network initiated the Pediatric Asthma Controller Trial (PACT) to compare the effectiveness of an ICS (fluticasone) and LABA (salmeterol) combination regimen to a regimen of the ICS alone and a regimen of a LTRA (montelukast) in controlling asthma.

Participants

Inclusion criteria were physician-diagnosed asthma, age 6 to less than 14 years, ability to perform reproducible spirometry, an FEV₁ (measured more than 4 hours since the most recent use of a bronchodilator) ≥80% predicted normal at screening and ≥70% predicted normal at randomization, and a methacholine FEV₁ PC₂₀ ≤12.5 mg/mL.

285 participants were randomized, with 252 completing the trial. 96 participants were randomized to the fluticasone monotherapy group, 94 participants were randomized to the PACT combination group, and 95 participants were randomized to the montelukast group. There were no statistically significant differences in withdrawals across groups.

Design

CARE-PACT was a double-blind, randomized, parallel, multi-center study. Within each center, a stratified randomization scheme was applied on the basis of bronchodilator response (<12% or ≥12% change in FEV₁), race (white or nonwhite), and methacholine FEV₁ PC₂₀ (<2 or ≥2 mg/mL).

All children were enrolled in a run-in period of 2 to 4 weeks, during which they received a morning and evening placebo Diskus, an evening placebo capsule, and open-label albuterol metered dose inhaler (MDI) as rescue. After the run-in, participants were assigned to 1 of 3 treatments: fluticasone propionate 100 μg morning and 100 μg evening plus placebo oral drug in the evening (hereafter referred to as fluticasone monotherapy); fluticasone propionate 100 μg/salmeterol 50 μg in the morning and salmeterol 50 μg in the evening plus placebo oral drug in the evening (hereafter referred to as PACT combination); or placebo Diskus in the morning and placebo Diskus in the evening plus montelukast 5 mg in the evening (hereafter referred to as montelukast). A standardized prednisone course was initiated in all treatment groups for an asthma exacerbation if predetermined criteria were met.

Electronic peak expiratory flow (PEF) measurements, asthma symptom scores, and albuterol use were recorded manually in diaries twice daily. Adherence to inhaled medication was estimated from the Diskus dose indicator, and oral medication adherence was assessed on the basis of capsule count and an Electronic Drug Exposure Monitor. During the 12 months of treatment, participants were evaluated at visits at intervals of 6 to 12 weeks. Methacholine FEV₁ PC₂₀ was performed at week 48 and maximal postbronchodilator spirometry at week 36.

The primary outcome was the percent of asthma control days during the 48-week treatment period. Secondary outcomes included percent of episode-free days (an asthma control day plus daily peak flows ≥80% of personal best), number of exacerbations requiring prednisone and time to the first exacerbation requiring prednisone, time to treatment failure, the 7-item Asthma Control Questionnaire (ACQ), pulmonary function and growth.

Conclusions

In school-aged children with mild to moderate asthma, both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control.

Sorkness CA, Lemanske RF, Mauger DT, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller Trial. J Allergy Clin Immunol. 2007;119(1):64-72. doi:10.1016/j.jaci.2006.09.042

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