Asthma
Conditions
Brief summary
This study will attempt to find out if the addition of an intravenous form of a drug that is already used for treating asthma in children will help resolve asthma attacks faster than using the current standard care alone.
Detailed description
The duration of treatment is a one time dose.
Interventions
DRUGmontelukast sodium
Montelukast IV 5.25 mg lyophilized (reconstituted in 20 mL of 3.3% dextrose/0.3% sodium chloride) for a study approximately 120 minutes in duration
DRUGComparator: placebo (unspecified)
Pbo for a study approximately 120 minutes in duration
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* Children 6-14 years of age seeking treatment in emergency departments with acute asthma attacks
Exclusion criteria
* Other respiratory conditions (including congenital lung abnormalities) or other acute illnesses that would complicate current treatment and response for asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in FEV1 (Forced Expiratory Volume in 1 Second) Over the First 60 Minutes After Administration | Baseline and (time weighted average over) 60 Minutes | Improvement in FEV1 as the time-weighted average change from baseline over 60 minutes following the end of study drug administration. Time-weighted average of the changes from baseline obtained over the 60 minutes (at 60, 45, 30 and 15) with the time interval between any measurement and the measurement prior to it used as the weighting factor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours) | 120 minutes | Treatment Failure is defined as a.) patients who required hospitalization, or b.) patients for whom a decision to discharge home has not been reached by 2 hours following the end of study drug administration. |
| Time-Weighted Average Change in FEV1 Over 45 Minutes Following the End of Study Drug Administration | Baseline and (time-weighed average over) 45 Minutes | Improvement in FEV1 as time-weighted average change from baseline over 45 minutes following the end of study drug administration: Time-weighted average of the changes from baseline obtained over the 45 minutes (at 45, 30 and 15) with the time interval between any measurement and the measurement prior to it used as the weighting factor. |
| Change From Baseline in Modified Pulmonary Index [mPI] Score | Baseline and 60 minutes | Change from baseline in modified pulmonary index \[mPI\] score assessed 60 minutes following the end of study drug administration. mPI questionnaire scores each component on a scale of 0 to 3 (low to high) with a total possible score of 12. The components are respiratory rate, wheezing, prolongation of expiration (Inspiratory:Expiratory ratio), and accessory muscle use. |
| Change in FEV1 After 15 Minutes Following the End of Study Drug Administration | Baseline and 15 Minutes | Improvement in FEV1 as the time-weighted average change from baseline over the first 15 minutes following the end of study drug administration. Change = 15 minutes value minus Baseline value |
| Total Dose of β-agonist Administered Per Patient Over a Period of 2 Hours Following the End of Study Drug Administration | 120 minutes | Median total dose of β-agonist administered per patient over a period of 2 hours following the end of study drug administration. |
| Time-Weighted Average Change in FEV1 Over 30 Minutes Following the End of Study Drug Administration | Baseline and (time-weighted average over) 30 Minutes | Improvement in FEV1 as the time-weighted average change from baseline over 30 minutes following the end of study drug administration. Time-weighted average of the changes from baseline obtained over the 30 minutes (at 30 and 15) with the time interval between any measurement and the measurement prior to it used as the weighting factor. |
Participant flow
Recruitment details
Phase III World Wide (U.S., Europe, Asia, South America, and Lithuania) Multicenter Study. Study Start Date: July 2005 Primary Completion Date: March 2008 Study Completion Date: March 2008
Participants by arm
| Arm | Count |
|---|---|
| Montelukast Intravenous (IV) 5.25 mg | 145 |
| Placebo | 131 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Did not meet Inclusion Criteria | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Montelukast Intravenous (IV) 5.25 mg |
|---|---|---|---|
| Age, Continuous | 8.9 years STANDARD_DEVIATION 2.32 | 9.1 years STANDARD_DEVIATION 2.34 | 9.2 years STANDARD_DEVIATION 2.36 |
| Baseline FEV 1 (L) | 1.00 Liters STANDARD_DEVIATION 0.5 | 1.0 Liters STANDARD_DEVIATION 0.5 | 1.06 Liters STANDARD_DEVIATION 0.5 |
| Baseline FEV1 (Percent predicted) | 50.6 Percent STANDARD_DEVIATION 17.4 | 51.2 Percent STANDARD_DEVIATION 17.1 | 51.8 Percent STANDARD_DEVIATION 16.8 |
| Race/Ethnicity Asian | 18 participants | 36 participants | 18 participants |
| Race/Ethnicity Black | 16 participants | 34 participants | 18 participants |
| Race/Ethnicity Hispanic | 53 participants | 112 participants | 59 participants |
| Race/Ethnicity Multi-Racial | 27 participants | 61 participants | 34 participants |
| Race/Ethnicity Other | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity White (Non-Hispanic) | 16 participants | 32 participants | 16 participants |
| Sex: Female, Male Female | 50 Participants | 105 Participants | 55 Participants |
| Sex: Female, Male Male | 81 Participants | 171 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / — | 21 / — |
| serious Total, serious adverse events | 2 / — | 2 / — |
Outcome results
Primary
Improvement in FEV1 (Forced Expiratory Volume in 1 Second) Over the First 60 Minutes After Administration
Improvement in FEV1 as the time-weighted average change from baseline over 60 minutes following the end of study drug administration. Time-weighted average of the changes from baseline obtained over the 60 minutes (at 60, 45, 30 and 15) with the time interval between any measurement and the measurement prior to it used as the weighting factor.
Time frame: Baseline and (time weighted average over) 60 Minutes
Population: Full Analysis Set (FAS). The FAS population includes all randomized patients who received double-blind study drug, and with efficacy measurements both at baseline and at least one time point over the time interval considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Improvement in FEV1 (Forced Expiratory Volume in 1 Second) Over the First 60 Minutes After Administration | 0.08 Liters |
| Placebo | Improvement in FEV1 (Forced Expiratory Volume in 1 Second) Over the First 60 Minutes After Administration | 0.07 Liters |
p-value: 0.77595% CI: [-0.06, 0.08]ANCOVA
Secondary
Change From Baseline in Modified Pulmonary Index [mPI] Score
Change from baseline in modified pulmonary index \[mPI\] score assessed 60 minutes following the end of study drug administration. mPI questionnaire scores each component on a scale of 0 to 3 (low to high) with a total possible score of 12. The components are respiratory rate, wheezing, prolongation of expiration (Inspiratory:Expiratory ratio), and accessory muscle use.
Time frame: Baseline and 60 minutes
Population: Full Analysis Set (FAS). The FAS population includes all randomized patients who received double-blind study drug, and with efficacy measurements both at baseline and at least one time point over the time interval considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Change From Baseline in Modified Pulmonary Index [mPI] Score | -2.95 Score on a scale |
| Placebo | Change From Baseline in Modified Pulmonary Index [mPI] Score | -2.96 Score on a scale |
p-value: 0.93195% CI: [-0.41, 0.45]ANCOVA
Secondary
Change in FEV1 After 15 Minutes Following the End of Study Drug Administration
Improvement in FEV1 as the time-weighted average change from baseline over the first 15 minutes following the end of study drug administration. Change = 15 minutes value minus Baseline value
Time frame: Baseline and 15 Minutes
Population: Full Analysis Set (FAS). The FAS population includes all randomized patients who received double-blind study drug, and with efficacy measurements both at baseline and at least one time point over the time interval considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Change in FEV1 After 15 Minutes Following the End of Study Drug Administration | 0.06 Liters |
| Placebo | Change in FEV1 After 15 Minutes Following the End of Study Drug Administration | 0.01 Liters |
p-value: 0.17395% CI: [-0.02, 0.11]ANCOVA
Secondary
Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours)
Treatment Failure is defined as a.) patients who required hospitalization, or b.) patients for whom a decision to discharge home has not been reached by 2 hours following the end of study drug administration.
Time frame: 120 minutes
Population: Full Analysis Set (FAS). At least one post-randomization measurement obtained subsequent to at least one dose of study treatment was required for inclusion in the analysis of treatment failure endpoint. Baseline FEV1 measurement was also required to assess this endpoint since it was included in the model.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours) | Hospitalization | 28 Participants |
| Montelukast Intravenous (IV) 5.25 mg | Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours) | Decision to Discharge Home not Reached by 2 Hours | 37 Participants |
| Placebo | Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours) | Hospitalization | 33 Participants |
| Placebo | Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours) | Decision to Discharge Home not Reached by 2 Hours | 26 Participants |
p-value: 0.97595% CI: [0.61, 1.61]Regression, Logistic
Secondary
Time-Weighted Average Change in FEV1 Over 30 Minutes Following the End of Study Drug Administration
Improvement in FEV1 as the time-weighted average change from baseline over 30 minutes following the end of study drug administration. Time-weighted average of the changes from baseline obtained over the 30 minutes (at 30 and 15) with the time interval between any measurement and the measurement prior to it used as the weighting factor.
Time frame: Baseline and (time-weighted average over) 30 Minutes
Population: Full Analysis Set (FAS). The FAS population includes all randomized patients who received double-blind study drug, and with efficacy measurements both at baseline and at least one time point over the time interval considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Time-Weighted Average Change in FEV1 Over 30 Minutes Following the End of Study Drug Administration | 0.06 Liters |
| Placebo | Time-Weighted Average Change in FEV1 Over 30 Minutes Following the End of Study Drug Administration | 0.05 Liters |
p-value: 0.77495% CI: [-0.06, 0.08]ANCOVA
Secondary
Time-Weighted Average Change in FEV1 Over 45 Minutes Following the End of Study Drug Administration
Improvement in FEV1 as time-weighted average change from baseline over 45 minutes following the end of study drug administration: Time-weighted average of the changes from baseline obtained over the 45 minutes (at 45, 30 and 15) with the time interval between any measurement and the measurement prior to it used as the weighting factor.
Time frame: Baseline and (time-weighed average over) 45 Minutes
Population: Full Analysis Set (FAS). The FAS population includes all randomized patients who received double-blind study drug, and with efficacy measurements both at baseline and at least one time point over the time interval considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Time-Weighted Average Change in FEV1 Over 45 Minutes Following the End of Study Drug Administration | 0.07 Liters |
| Placebo | Time-Weighted Average Change in FEV1 Over 45 Minutes Following the End of Study Drug Administration | 0.05 Liters |
p-value: 0.61295% CI: [-0.05, 0.09]ANCOVA
Secondary
Total Dose of β-agonist Administered Per Patient Over a Period of 2 Hours Following the End of Study Drug Administration
Median total dose of β-agonist administered per patient over a period of 2 hours following the end of study drug administration.
Time frame: 120 minutes
Population: At least one post-randomization measurement obtained subsequent to at least one dose of study treatment was required for inclusion in the analysis of total doses of Beta-Agonist (mg) endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Montelukast Intravenous (IV) 5.25 mg | Total Dose of β-agonist Administered Per Patient Over a Period of 2 Hours Following the End of Study Drug Administration | 1.0 mg |
| Placebo | Total Dose of β-agonist Administered Per Patient Over a Period of 2 Hours Following the End of Study Drug Administration | 0.6 mg |
p-value: 0.58ANCOVA