Oral montelukast treatment of preschool-aged children with acute asthma. Pilot study of oral montelukast added to standard therapy for acute asthma exacerbations in children aged 6 to 14 years. Zafirlukast treatment for acute asthma: evaluation in a randomized, double-blind, multicenter trial. Effect of addition of single dose of oral montelukast to standard treatment in acute moderate to severe asthma in children between 5 and 15 years of age: a randomised, double-blind, placebo controlled trial. A randomized controlled trial of intravenous montelukast in acute asthma. A randomized, placebo-controlled study of intravenous montelukast in children with acute asthma. Effects of oral montelukast on airway function in acute asthma.
Increased amounts of cysteinyl leukotrienes have been demonstrated in urine samples from asthmatic patients, particularly during exacerbations of asthma. Although the use of leukotriene receptor antagonists has been recommended in the treatment of chronic asthma, no guidelines are available regarding their use in the treatment of acute asthma.
                To investigate the safety and effectiveness of a 4-mg tablet of oral montelukast in addition to short-acting beta2-agonist bronchodilator as the initial treatment in mild to moderate asthma exacerbations in children between 2 and 5 years old.
                Fifty-one patients who were experiencing mild to moderate asthma exacerbation were included in a randomized, double-blind, placebo-controlled, parallel-group study. Each patient received either a 4-mg tablet of montelukast or placebo in addition to inhaled salbutamol and were followed up for 4 hours. The pulmonary index score, respiratory rate, and pulse were determined at baseline and throughout 4 hours after administration.
                Compared with placebo, the pulmonary index scores and respiratory rates were significantly lower in the montelukast group starting at 90 minutes (P = .01). This difference persisted at 120, 180, and 240 minutes of the study (P = .008, P = .02, and P = .048, respectively). At the end of the first hour of treatment, oral steroid need was 20.8% and 38.5% in patients randomized to the montelukast and placebo groups, respectively (P = .22). Hospitalization rates were not different between the 2 treatment groups.
                A single 4-mg tablet of montelukast had the potential to provide additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting beta2-agonist bronchodilators as the initial treatment. We hypothesized that children with moderate acute asthma exacerbations receiving oral montelukast with standard therapy will have at least 12% greater forced expiratory volume in 1 second (FEV1) improvement in 3 hours than those receiving standard therapy alone.
                In this randomized, double-blind, placebo-controlled study, we enrolled emergency patients aged 6 to 14 years with moderate acute asthma exacerbations (peak expiratory flow rate, 40%-70% predicted). Subjects received montelukast 5 mg or placebo orally then standard therapy. We measured FEV1 before study medication administration and hourly for 3 hours. The primary outcome was FEV1% predicted change at 3 hours.
                At the time of the planned interim analysis, we had enrolled 27 subjects; 23 (11 montelukast, 12 placebo) had a complete FEV1 data. Both groups had similar mean FEV1 increases at 3 hours (mean [SD]: montelukast = 16.8% [11.4%], placebo = 19.9% [12.1%]; 95% confidence interval for difference = -12.22% to 5.95%). Based on further analysis, we determined that enrollment of the planned sample was unlikely to significantly change the results. If our study hypothesis were true, the montelukast group mean FEV1 increase should be 32% or greater. The probabilities were low that the montelukast sample could be drawn from a normally distributed population with a mean of 32% and that subsequently enrolled montelukast subjects would have sufficient FEV1 improvements to attain a mean of greater than 32%.
                Based on these results, for children aged 6 to 14 years with moderate acute asthma exacerbations, oral montelukast (5 mg) added to standard therapy as in this design is unlikely to result in additional FEV1 improvements in 3 hours. Acute asthma causes nearly 2 million hospital emergency department (ED) visits in the United States annually, and hospitalization after an ED visit and relapse after ED discharge are common.
                To evaluate the adding of therapy with zafirlukast to standardized care for patients with acute asthma in the ED and a 28-day follow-up period.
                A total of 641 patients presenting to the ED with acute asthma were randomized to receive either single-dose zafirlukast, 160 mg (Z160) [162 patients], zafirlukast, 20 mg (Z20) [158 patients]), or placebo (321 patients) as adjunct treatment to standard care in this double-blind, multicenter trial. Assessments, including spirometry and symptom scores, were obtained before each albuterol treatment and at 4 h. Patients who were discharged from the ED after 4 h continued outpatient therapy over a 28-day period and received either Z20 bid (276 patients) or placebo (270 patients) in addition to prednisone, albuterol, and their previous asthma medications. FEV(1) was measured at clinic visits on days 10 and 28. Patients recorded outpatient clinical data twice daily on a home diary card.
                the effect of zafirlukast on relapse after ED discharge. Other assessments were the rate of extended care (ie, ED stay for > 4 h or hospitalization), FEV(1), and symptoms.
                At the end of the outpatient period, 65 of 276 patients (23.6%) treated with zafirlukast and 78 of 270 patients (28.9%) treated with placebo relapsed (p = 0.047; absolute reduction, 5.3%; relative reduction, 18.3%). At the end of the ED period, 16 of 162 patients (9.9%) treated with Z160, 26 of 158 patients (16.5%) treated with Z20, and 48 of 321 patients (15.0%) treated with placebo required extended care (p = 0.052; absolute reduction with Z160 compared to placebo, 5.1%; relative reduction, 34%). These findings were supported by a significant improvement in FEV(1) and dyspnea in the ED with the use of Z160 therapy, and by greater improvement in FEV(1) and symptoms during the outpatient period for patients treated with Z20.
                When added to standardized care, therapy with Z20 bid reduced the risk of relapse compared with placebo over a 28-day treatment period. One dose of Z160 in the ED also reduced the rate of extended care. To study the effect of the addition of a single dose of oral montelukast to standard therapy in acute moderate to severe asthma.
                Double-blind randomised controlled trial. Setting Emergency room/outpatient paediatric services of a tertiary care hospital.
                Children aged 5-15 years (without prior use of montelukast) with acute moderate to severe asthma exacerbation, as defined using Modified Pulmonary Index Score (MPIS) > or =9, were enrolled.
                Children received montelukast (5-12 years: 5 mg and >12 years: 10 mg) or placebo orally in addition to the standard therapy. MPIS and forced expiratory volume in 1 second (FEV(1)) were recorded before administering study medication and thereafter, hourly for 4 hours.
                The primary outcome was decrease in MPIS to less than 9 at the end of 4 hours.
                117 children (60 in montelukast group and 57 in placebo group) were enrolled in the study. The number of children with decrease in MPIS to less than 9 at 4 hours was 33 (55%) in the montelukast group and 36 (63.2%) in the placebo group (p=0.37). There was significant improvement in MPIS and FEV(1) within both the groups from baseline to the end of 4 hours. No differences in side effects and hospitalisation rates were noticed between the two groups.
                Single dose oral montelukast added to standard therapy of inhaled bronchodilators and systemic glucocorticoids did not provide additional clinical benefit in children with acute moderate to severe asthma. Trial registration number The trial was registered at the http://clinicaltrials.gov site (trial ID: NCT00565955). Many patients with acute asthma do not respond adequately to currently accepted therapy, including oxygen, beta-agonists, and corticosteroids. Leukotriene receptor antagonists such as montelukast have demonstrated efficacy in chronic asthma, but their efficacy in acute asthma is unknown. In this randomized, double-blind, parallel-group pilot study, adults with moderate to severe acute asthma received standard therapy plus either intravenous montelukast (7 or 14 mg) or matching placebo. A total of 201 patients were randomized, and 194 had complete data available for analysis. There was no difference in FEV1 response between the 7- and 14-mg montelukast groups. Montelukast improved FEV1 over the first 20 minutes after intravenous administration (mean percentage change from prerandomization baseline, 14.8% versus 3.6% for the pooled montelukast and placebo treatment groups, respectively; p = 0.007). This benefit was observed at 10 minutes and over 2 hours after intravenous therapy. Patients treated with montelukast tended to receive less beta-agonists and have fewer treatment failures than patients receiving placebo. The tolerability profile for montelukast was similar to that observed for placebo, and no unexpected adverse experiences were observed. We conclude that intravenous montelukast in addition to standard therapy causes rapid benefit and is well tolerated in adults with acute asthma. Up to 30% of patients require hospitalization for acute asthma despite standard therapy in the emergency department. In adults, intravenous montelukast added to standard therapy significantly improved forced expiratory volume in 1 second (FEV1) and reduced hospital admissions compared with standard therapy alone.
                To evaluate the efficacy of intravenous montelukast added to standard therapy in children with acute asthma.
                This was a randomized, double-blind, placebo-controlled, multicenter study of children aged 6 to 14 years conducted from August 25, 2005 to March 17, 2008. Patients with an FEV1 of 75% or less of the predicted value after up to 120 minutes of standard therapy (e.g., oxygen, albuterol, inhaled anticholinergics, and systemic oral corticosteroids) were randomized to intravenous montelukast, 5.25 mg (n=145), or placebo (n=131) added to standard therapy. The primary end point was the time-weighted average change in FEV1 during 60 minutes (deltaFEV1[0-60 min]). Secondary end points included the percentage of patients in whom treatment failed (patients who required hospitalization or for whom a decision to discharge was not reached within 2 hours after drug administration) and the change from baseline in modified pulmonary index score after 60 minutes of treatment.
                Montelukast was not significantly more effective than placebo for deltaFEV1[0-60 min] when added to standard therapy (0.08 vs. 0.07 L; least squares mean, 0.01; 95% confidence interval, -0.06 to 0.08; P = .78). No significant differences were found in the percentages of patients in whom treatment failed or the modified pulmonary index score after 60 minutes. Both treatments were well tolerated.
                In this study of children with acute asthma, intravenous montelukast was not significantly better than placebo in improving FEV1, symptoms, or overall hospital course. Montelukast, a specific cysteinyl leukotriene receptor antagonist, has been shown to improve pulmonary function within 1 h of ingestion. This study was undertaken to compare the effects on peak expiratory flow rate (PEFR) of oral montelukast added to intravenous steroid, intravenous steroid alone and placebo during the 24 h period following administration. Seventy asthmatic patients (FEV1 40-80% predicted and > or = 15% improvement after inhaled beta agonist) were enrolled in a single blind study to receive oral montelukast (10 mg) plus intravenous prednisolone (1 mg/kg), intravenous prednisolone (1 mg/kg) or placebo in a randomised fashion. The patients received one ofthe above three groups of medication before any other treatments. This was immediately followed by the aerosol treatments of 100 mcg of terbutaline sulphate divided into three doses during 1 h as described in the consensus statement. Thereafter, patients were observed for 24 h to document the effects on PEFR, Borg dyspnoea score and need for rescue medication. The primary end point was percentage change at different time points. Secondary end points were Borg dyspnoea score and use of rescue medication. Compared with placebo, montelukast added to the prednisolone group and the prednisolone alone group had significant percentage change from baseline in PEFR in the entire 24 h period (P<0.05). The difference in PEFR between montelukast plus prednisolone group and prednisolone group favoured the montelukast plus prednisolone group but did not reach statistical significance. Furthermore, montelukast plus prednisolone group required less inhaled short-acting beta agonistthan other two groups. The results of this study indicate that adding montelukast to steroid in acute asthma may have some additive improvement in lung functions.
Presently, the available evidence does not support routine use of oral LTRAs in acute asthma. Further studies are required to assess whether intravenous treatment can reduce the risk of hospital admission, and what the most appropriate dose regimen is. Additional research is also needed into safety and efficacy of additional doses for those on maintenance therapy, and larger paediatric trials are required to allow subgroup analysis. Prolonged studies would be required to establish other health economic outcomes in admitted patients.