Table 2.
Randomized control trials of effectiveness and clinical efficacy of montelukast, with references listed in chronological order according to the year of publication
| Population | Design | Efficacy and adverse effects | Remarks | References |
|---|---|---|---|---|
| 16–49 years | Randomized, placebo-controlled trial, nonsmoking adults with postinfectious cough from 25 general practices in England. 276 patients to montelukast (n=137) or placebo (n=139); 70 (25%) patients had laboratory-confirmed pertussis | Montelukast is not an effective treatment for postinfectious cough in terms of quality of life and clinical parameters. Increased mucus production (montelukast, n=6; placebo, n=2), gastrointestinal disturbance (montelukast, n=3; placebo, n=5), and headache documented. | Multicenter trial documented no clinical efficacy. | 74* |
| 6–14 years | Randomized, double-blind, placebo-controlled, parallel study | No evidence that adding salmeterol or montelukast to ICSs can reduce the number of exacerbations in children with uncontrolled asthma. No significant adverse effects. | Clinical, laboratory, and quality of life assessments. | 99 |
| 18–65 years | Randomized, comparative, multicenter clinical trial | Zileuton ER seems to be more efficacious than montelukast and well tolerated for the treatment of mild to moderate chronic persistent asthma in adult patient population. No adverse effects. | Another leukotriene. | 100* |
| >16 years, mean (SD) 52 (18.5) years | Randomized, double-blind, placebo-controlled trial in 100 patients | No benefit of addition of oral montelukast over conventional treatment in the management of acute asthma attack. No adverse effects. | No benefit in older children. | 55* |
| 6–18 years | Randomized, placebo-controlled, double-blinded trial with montelukast or ICS of 24 patients | FEV1 improvement only. No adverse effects mentioned. | Small study; only FEV1 assessed. | 70* |
| Adults | Three parallel, 6-month, double-blind treatment arms; 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. | In a population of asthmatic patients actively smoking cigarettes, both 10 mg/day montelukast and 250 mg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo. No difference between montelukast and ICS in terms of effectiveness or side effects. | Only evaluated asthma control in days. An alternative treatment for smokers. | 75* |
| Adults | Randomized placebo control of 87 patients | Additional administration of oral montelukast results in a significantly higher PEF the morning after admission than that achievable with current standard treatment in acute asthma. No adverse effects. | Not-intention to treat. Only peak flow improvement demonstrated. | 101* |
| 4–14 years | Randomized, double-blind, placebo-controlled, two-period crossover study (n=66) | FEV1 assessment. Single-dose montelukast provided rapid and sustained EIB attenuation in children. No adverse effects mentioned. | Small study; only FEV1 assessed. | 71* |
| 5–18 years | Randomized, double-blind, parallel-group, 12-month pilot trial | ICS a better choice as initial asthma therapy than montelukast in children with newly diagnosed asthma. No adverse effects. | In 60 children montelukast generally inferior. | 102 |
| Children 5–12 years | Double-blind, randomized placebo controlled trial on 117 children | 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. No adverse effects. | In-patients with moderate to severe asthma attacks only. | 103* |
| 6–14 years | Randomized, double-blind, double-dummy, multicenter, two-period, 4-week, crossover study; 154 patients randomized, 145 completed | Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment. No adverse effects. | FEV1 response only. Not intention-to-treat. | 72* |
| Adults | Randomized double-blind trial of 20 asthmatic subjects with documented hyperpnea-induced bronchoconstriction | FEV1 and urinary biomarkers. No significant effects. Fish oil supplementation should be considered as an alternative treatment for EIB. Montelukast useful but not superior. | Effects on FEV1 and urinary biomarkers. | 73* |
| 6–14 years | Randomized, double-blind, placebo-controlled study | Interim analysis 27 patients. Moderate acute asthma exacerbations, oral montelukast (5 mg) added to standard therapy is unlikely to result in additional FEV1 improvements in 3 hours. | Small sample size interim study with no efficacy. | 104* |
| 2–14 years | Double-blind, randomized, placebo-controlled trial on 194 asthmatic children | Montelukast added to usual treatment reduced the risk of worsened asthma symptoms and unscheduled physician visits during the predictable annual September asthma epidemic. | Some clinical efficacy demonstrated. | 105* |
| Adults | Multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast | Primary outcome was change in prebronchodilator FEV1 in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein in both smokers and nonsmokers but increased FEV1 (170 mL, P=0.0003) only in nonsmokers. Montelukast significantly increased morning peak flow in smokers (12.6 L/min, P=0.002) but not in nonsmokers. | Small sample sizes but clinical efficacy demonstrated. | 76* |
| Children and adults | Systematic literature review of eleven clinical studies | Combination therapy with ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Montelukast is inferior. No adverse effects on montelukast. | Evaluates combination therapy with ICS plus LABA. | 92 |
| 2–5 years | Randomized, double-blind, placebo-controlled, parallel-group of 51 patients | A single 4 mg tablet of montelukast provided additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting beta 2-agonist bronchodilators as the initial treatment. No adverse effects. | Small study. Demonstrate efficacy in mild to moderate disease in preschool children. | 106* |
| 6–24 months | Randomized, double-blind, placebo-controlled, parallel-group | In 256 patients, no demonstrable efficacy or adverse effects between montelukast and placebo. | Not 1:1 randomization or intention-to-treat. Large sample size. | 58* |
| 2–5 years | Double-blind, multicenter, multinational study at 93 centers worldwide (n=689). | Montelukast improves multiple clinical parameters of asthma control, without important adverse effects. | Large multicenter study. Efficacy of montelukast demonstrated. | 57* |
| Mean (SD) age 10.4 (2.2) years | Multicenter, randomized, double-blind, crossover study (n=279) | Improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days. No adverse effects. | Added on efficacy demonstrated clinically. | 59* |
Note:
*
Note: Additional references identified.
Abbreviations: EIB, exercise-induced bronchoconstriction; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LABA, long-acting beta 2-agonist; PC(20), concentration to produce a 20% fall in FEV1 from baseline; PEF, peak expiratory flow; SD, standard deviation.