Asthma
Conditions
Brief summary
This is a year-long study evaluating the efficacy of both daily and intermittent treatment of asthma in children who experience symptoms episodically (i.e., seasonally, usually in the context of upper respiratory tract infection).
Interventions
DRUGmontelukast sodium
Montelukast 4 mg (or 5 mg, depending on age of patient) qd + episode driven supplemental Pbo qd for 12 days for a 52-wk treatment period.
DRUGComparator: Placebo (unspecified)
Placebo (Pbo) qd + episode driven supplemental Pbo for 12 days for a 52-wk treatment period.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 5 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 6 months to 5 years with episodic (periodic) asthma
Exclusion criteria
* Patients who are not in otherwise good health * Patients who have persistent asthma (continual asthma symptoms)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Asthma Episodes Culminating in Asthma Attack Over the 1-year Treatment Period | 1-year treatment period | The rate per year of asthma episodes culminating in an asthma attack for each of the 3 treatment groups. Asthma attacks were defined as respiratory symptoms requiring healthcare resource utilization (HRU), which comprised unscheduled visits to a physician or emergency department, treatment with corticosteroids (oral, rectal, or inhaled), or hospitalization. Each day during an episode, the patient's legal guardian recorded all the HRU that was required specifically for breathing problems. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Average of Wheeze and Difficulty Breathing in the 3 Days Prior to Start of an Asthma Attack Within an Asthma Episode | 1 Year | Each day during an asthma episode, the patient's legal guardian was asked to rate each of the symptoms of wheeze and difficulty breathing on a 6-point scale (Scale 0 (best) to 5 (worst)). The average of the individual symptom scores on each of the 3 days prior to an asthma attack was reported. If a patient had multiple episodes during 1 year, the symptom scores were averaged across all the episodes. |
| Daily Average of the Mean Symptom Scores (Wheeze, Difficulty Breathing, Interference With Activity, and Daytime Cough) Assessed Over the 12-day Treatment Period of Asthma Episodes | 1 Year | Each day during an asthma episode, the patient's legal guardian was asked to rate each of the symptoms of Wheeze, Difficulty Breathing, Interference with Activity, and Daytime Cough on a 6-point scale (Scale 0 (best) to 5 (worst)). The average of the individual symptom scores on each of the 12 days of intermittent treatment for an episode (before the first attack) was reported. If a patient had multiple episodes over 1 year, the symptom scores were averaged across all the episodes. |
Participant flow
Recruitment details
Patients were recruited from 111 centers worldwide. Patient screening began 16-Oct-2006 and the first patient was randomized on 3-Nov-2006. The last patient's last visit was completed on 12-Aug-2009.
Pre-assignment details
1979 screened; 208 excluded. Randomized patients met the following criteria: age 6-71 months, a history of episodic asthma symptoms that ranged between 2 and 6 episodes, depending on age, that were separated in time by periods without asthma symptoms. Patients had at least 1 corticosteroid treatment or were hospitalized for asthma at least 1 time.
Participants by arm
| Arm | Count |
|---|---|
| Daily Montelukast Patients were randomized to receive montelukast 4 mg (tablets or oral granules, depending on patient age) once daily at bedtime for 52 weeks plus intermittent 12-day courses of matching-image placebo (tablets or oral granules) once daily at bedtime (a course was initiated as needed for symptoms of imminent respiratory infection or episode of breathing problems) during the 52-week study period. | 589 |
| Intermittent Montelukast Patients were randomized to receive matching-image placebo to montelukast 4 mg (tablets or oral granules, depending on age) once daily at bedtime for 52 weeks plus intermittent 12-day courses of montelukast 4 mg (tablets or oral granules) once daily at bedtime (a course was initiated as needed for symptoms of imminent respiratory infection or episode of breathing problems) during the 52-week study period. | 591 |
| Placebo Patients were randomized to receive matching-image placebo to montelukast 4 mg (tablets or oral granules, depending on age) once daily at bedtime for 52 weeks plus intermittent 12-day courses of matching-image placebo (tablets or oral granules) once daily at bedtime (a course was initiated as needed for symptoms of imminent respiratory infection or episode of breathing problems) during the 52-week study period. | 591 |
| Total | 1,771 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 9 | 19 |
| Overall Study | Lack of Efficacy | 10 | 7 | 9 |
| Overall Study | Lost to Follow-up | 22 | 19 | 17 |
| Overall Study | Physician Decision | 9 | 17 | 14 |
| Overall Study | Progressive Disease | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 21 | 24 | 19 |
| Overall Study | Trial Terminated | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 25 | 25 | 19 |
Baseline characteristics
| Characteristic | Intermittent Montelukast | Placebo | Total | Daily Montelukast |
|---|---|---|---|---|
| Age, Continuous | 39.5 Months | 39.3 Months | 39.2 Months | 39.0 Months |
| Sex: Female, Male Female | 226 Participants | 238 Participants | 703 Participants | 239 Participants |
| Sex: Female, Male Male | 365 Participants | 353 Participants | 1068 Participants | 350 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 481 / 584 | 506 / 588 | 486 / 585 |
| serious Total, serious adverse events | 28 / 584 | 41 / 588 | 33 / 585 |
Outcome results
Primary
Number of Asthma Episodes Culminating in Asthma Attack Over the 1-year Treatment Period
The rate per year of asthma episodes culminating in an asthma attack for each of the 3 treatment groups. Asthma attacks were defined as respiratory symptoms requiring healthcare resource utilization (HRU), which comprised unscheduled visits to a physician or emergency department, treatment with corticosteroids (oral, rectal, or inhaled), or hospitalization. Each day during an episode, the patient's legal guardian recorded all the HRU that was required specifically for breathing problems.
Time frame: 1-year treatment period
Population: Full Analysis Set (FAS): all randomized patients who took at least one dose of blinded study drug. Of 1771 patients randomized, 5 never took study drug and 9 were not included due to Good Clinical Practice compliance concerns. Therefore, 1757 patients were included in the FAS population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Daily Montelukast | Number of Asthma Episodes Culminating in Asthma Attack Over the 1-year Treatment Period | 0.99 Asthma attacks within episodes per year |
| Intermittent Montelukast | Number of Asthma Episodes Culminating in Asthma Attack Over the 1-year Treatment Period | 1.06 Asthma attacks within episodes per year |
| Placebo | Number of Asthma Episodes Culminating in Asthma Attack Over the 1-year Treatment Period | 1.05 Asthma attacks within episodes per year |
Comparison: The primary hypothesis stated that montelukast (daily regimen, or \[intermittent and daily regimens\]), compared with placebo, results in a decrease in the number of asthma episodes culminating in asthma attack in pediatric patients aged 6 months to 5 years with episodic asthma and treated over 1 year. A sample size of 450 evaluable patients per arm allowed the detection of a difference in rate of 23% with 90% power.p-value: 0.5195% CI: [-11.4, 19.6]Regression, Poisson
Comparison: The primary hypothesis stated that montelukast (daily regimen, or \[intermittent and daily regimens\]), compared with placebo, results in a decrease in the number of asthma episodes culminating in asthma attack in pediatric patients aged 6 months to 5 years with episodic asthma and treated over 1 year. A sample size of 450 evaluable patients per arm allowed the detection of a difference in rate of 23% with 90% power.p-value: 0.88495% CI: [-19.2, 14]Regression, Poisson
Secondary
Daily Average of the Mean Symptom Scores (Wheeze, Difficulty Breathing, Interference With Activity, and Daytime Cough) Assessed Over the 12-day Treatment Period of Asthma Episodes
Each day during an asthma episode, the patient's legal guardian was asked to rate each of the symptoms of Wheeze, Difficulty Breathing, Interference with Activity, and Daytime Cough on a 6-point scale (Scale 0 (best) to 5 (worst)). The average of the individual symptom scores on each of the 12 days of intermittent treatment for an episode (before the first attack) was reported. If a patient had multiple episodes over 1 year, the symptom scores were averaged across all the episodes.
Time frame: 1 Year
Population: Patients with at least one episode culminating in an attack were included; therefore, 1120 patients were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Daily Montelukast | Daily Average of the Mean Symptom Scores (Wheeze, Difficulty Breathing, Interference With Activity, and Daytime Cough) Assessed Over the 12-day Treatment Period of Asthma Episodes | 1.08 Units on a Scale |
| Intermittent Montelukast | Daily Average of the Mean Symptom Scores (Wheeze, Difficulty Breathing, Interference With Activity, and Daytime Cough) Assessed Over the 12-day Treatment Period of Asthma Episodes | 1.09 Units on a Scale |
| Placebo | Daily Average of the Mean Symptom Scores (Wheeze, Difficulty Breathing, Interference With Activity, and Daytime Cough) Assessed Over the 12-day Treatment Period of Asthma Episodes | 1.20 Units on a Scale |
Comparison: The secondary hypothesis stated that montelukast (daily regimen, or \[intermittent and daily regimens\]), compared with placebo, results in improvement of respiratory symptoms assessed over 3 days prior to asthma attacks, or assessed over the 12-day treatment period of asthma episodes in pediatric patients aged 6 months to 5 years with episodic asthma and treated over 1 year.p-value: 0.04595% CI: [-0.24, 0]ANOVA
Comparison: The secondary hypothesis stated that montelukast (daily regimen, or \[intermittent and daily regimens\]), compared with placebo, results in improvement of respiratory symptoms assessed over 3 days prior to asthma attacks, or assessed over the 12-day treatment period of asthma episodes in pediatric patients aged 6 months to 5 years with episodic asthma and treated over 1 year.p-value: 0.06195% CI: [-0.23, 0]ANOVA
Secondary
Daily Average of Wheeze and Difficulty Breathing in the 3 Days Prior to Start of an Asthma Attack Within an Asthma Episode
Each day during an asthma episode, the patient's legal guardian was asked to rate each of the symptoms of wheeze and difficulty breathing on a 6-point scale (Scale 0 (best) to 5 (worst)). The average of the individual symptom scores on each of the 3 days prior to an asthma attack was reported. If a patient had multiple episodes during 1 year, the symptom scores were averaged across all the episodes.
Time frame: 1 Year
Population: Only patients who experienced an asthma attack within an episode and did not start their intermittent study medication on the day of the attack could be included. Therefore, a total of 452 patients were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Daily Montelukast | Daily Average of Wheeze and Difficulty Breathing in the 3 Days Prior to Start of an Asthma Attack Within an Asthma Episode | 1.69 Units on a Scale |
| Intermittent Montelukast | Daily Average of Wheeze and Difficulty Breathing in the 3 Days Prior to Start of an Asthma Attack Within an Asthma Episode | 1.70 Units on a Scale |
| Placebo | Daily Average of Wheeze and Difficulty Breathing in the 3 Days Prior to Start of an Asthma Attack Within an Asthma Episode | 1.88 Units on a Scale |
Comparison: The secondary hypothesis stated that montelukast (daily regimen, or \[intermittent and daily regimens\]), compared with placebo, results in improvement of respiratory symptoms assessed over 3 days prior to asthma attacks, or assessed over the 12-day treatment period of asthma episodes in pediatric patients aged 6 months to 5 years with episodic asthma and treated over 1 year.p-value: 0.17695% CI: [-0.46, 0.09]ANOVA
Comparison: The secondary hypothesis stated that montelukast (daily regimen, or \[intermittent and daily regimens\]), compared with placebo, results in improvement of respiratory symptoms assessed over 3 days prior to asthma attacks, or assessed over the 12-day treatment period of asthma episodes in pediatric patients aged 6 months to 5 years with episodic asthma and treated over 1 year.p-value: 0.20295% CI: [-0.44, 0.09]ANOVA