Childhood Asthma Research and Education (CARE) Network Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid (CLIC)

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Accession Number

Study Type
Clinical Trial

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
January 2002-March 2003

NHLBI Division

Dataset(s) Last Updated
November 9, 2020

Clinical Trial URLs


Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No


To determine whether pediatric asthmatic patients respond to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) similarly or if patients who do not respond to one medication respond to the other.


Inhaled corticosteroids (ICSs) have been recognized as the preferred long-term control therapy in patients with persistent asthma, including children of all ages, with nonsteroid long-term control medications positioned as alternative choices. The preference for ICSs was based primarily on evidence from previous clinical trials; however, few studies had addressed the factors that determine the marked variability in response to asthma control therapy. It was unknown, for example, whether patients who did not respond well to one medication might respond to the other medication. The purpose of the CARE-CLIC trial was to identify patient features that could serve as indicators for selection of the medication most likely to achieve a favorable response in individual patients.


144 participants, ages 6-17 with mild-to-moderate asthma, were enrolled in the study. Of these, 126 participants successfully completed both treatment arms for the primary end point.

Participants must have exhibited reversible airflow obstruction (≥ 12% improvement in FEV1 following the maximal bronchodilator testing procedure with albuterol MDI) or a methacholine PC20 ≤ 12.5 mg/ml to qualify for study entry. Participants must have had no corticosteroid treatment within 4 weeks, no leukotriene-modifying agents within 2 weeks, and no history of respiratory tract infection within 4 weeks of enrollment. Children were excluded for severe asthma or FEV1 of less than 70% of predicted value.


Prior to randomization the following tests were collected: asthma history, allergen skin tests, blood total eosinophil counts , serum eosinophil cationic protein levels, serum total IgE levels, urinary leukotriene E4 levels, methacholine PC20 values, and exhaled nitric oxide levels were obtained.

After a 5 to 10-day assessment period, participants were randomized to 1 of 2 crossover treatment sequences. Each treatment period lasted 8 weeks and there was no washout period between the treatment periods. The two treatment groups were an active ICS, fluticasone propionate (100 μg per inhalation twice daily), or an active LTRA, montelukast (1 tablet at night, 5-mg tablet for participants aged 6 to 14 years of age and 10-mg tablet for those 15 to 18 years of age). During the active treatment period for one drug, the participant received a placebo for the alternative drug.

The primary outcome measured was percentage change in prebronchodilator FEV1 from baseline to the end of each treatment period. Additional parameters were assessed at visits performed every 4 weeks during the 16-week treatment phase. Electronic peak flow measurements and asthma symptom scores were recorded daily.


Defining response as improvement in FEV1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Although responses to fluticasone and montelukast varied considerably in children with asthma, children with lower pulmonary function or higher levels of markers associated with allergic inflammation should receive ICS therapy. Children without these indicators could receive a therapeutic trial of either ICS or LTRA.

Szefler SJ, Phillips BR, Martinez FD, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115(2):233-242. doi:10.1016/j.jaci.2004.11.014

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