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A Study of an Intravenous Drug in Pediatric Patients With Acute Asthma (0476-301)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00117338
Recruitment Status : Completed
First Posted : July 6, 2005
Results First Posted : August 11, 2009
Last Update Posted : April 6, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: montelukast sodium
Drug: Comparator: placebo (unspecified)
Enrollment 276
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
Pre-assignment Details  
Arm/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 145 131
Completed 140 127
Not Completed 5 4
Reason Not Completed
Adverse Event             0             1
Protocol Violation             3             2
Withdrawal by Subject             1             0
Did not meet Inclusion Criteria             1             0
Lack of Efficacy             0             1
Arm/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 145 131 276
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 145 participants 131 participants 276 participants
9.2  (2.36) 8.9  (2.32) 9.1  (2.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 131 participants 276 participants
Female
55
  37.9%
50
  38.2%
105
  38.0%
Male
90
  62.1%
81
  61.8%
171
  62.0%
Race/Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 145 participants 131 participants 276 participants
White (Non-Hispanic) 16 16 32
Black 18 16 34
Hispanic 59 53 112
Asian 18 18 36
Multi-Racial 34 27 61
Other 0 1 1
Baseline FEV 1 (L)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 145 participants 131 participants 276 participants
1.06  (0.5) 1.00  (0.5) 1.0  (0.5)
[1]
Measure Description:

Forced Expiratory Volume in one second, measured in Liters (FEV 1 (L))

A total of 4/276 (1—montelukast; 3—placebo) randomized patients were excluded from the Full Analysis Set (FAS) of the primary endpoint

Baseline FEV1 (Percent predicted)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 145 participants 131 participants 276 participants
51.8  (16.8) 50.6  (17.4) 51.2  (17.1)
[1]
Measure Description:

Percent of predicted baseline Forced Expiratory Volume in one second (FEV1)

A total of 4/276 (1—montelukast; 3—placebo) randomized patients were excluded from the Full Analysis Set (FAS) of the primary endpoint

1.Primary Outcome
Title Improvement in FEV1 (Forced Expiratory Volume in 1 Second) Over the First 60 Minutes After Administration
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 144 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.08
(0.02 to 0.13)
0.07
(0.01 to 1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.775
Comments [Not Specified]
Method ANCOVA
Comments Model terms: treatment, region (US, non-US) and baseline FEV1 as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval 95%
-0.06 to 0.08
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Modified Pulmonary Index [mPI] Score
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 143 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
-2.95
(-3.26 to -2.63)
-2.96
(-3.29 to -2.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.931
Comments [Not Specified]
Method ANCOVA
Comments Model terms: treatment, region (US, non-US) and baseline FEV1 as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval 95%
-0.41 to 0.45
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Treatment Failure (Hospitalization or Time to Decision to Discharge > 2 Hours)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 144 128
Measure Type: Number
Unit of Measure: Participants
Hospitalization 28 33
Decision to Discharge Home not Reached by 2 Hours 37 26
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.975
Comments [Not Specified]
Method Regression, Logistic
Comments Model terms: treatment and baseline FEV1 as covariate
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.99
Confidence Interval 95%
0.61 to 1.61
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time-Weighted Average Change in FEV1 Over 45 Minutes Following the End of Study Drug Administration
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 142 127
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.07
(0.02 to 0.12)
0.05
(0.00 to 0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.612
Comments [Not Specified]
Method ANCOVA
Comments Model terms: treatment, region (US, non-US) and baseline FEV1 as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval 95%
-0.05 to 0.09
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time-Weighted Average Change in FEV1 Over 30 Minutes Following the End of Study Drug Administration
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 140 125
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.06
(0.01 to 0.12)
0.05
(-0.00 to 0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.774
Comments [Not Specified]
Method ANCOVA
Comments Model terms: treatment, region (US, non-US) and baseline FEV1 as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval 95%
-0.06 to 0.08
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in FEV1 After 15 Minutes Following the End of Study Drug Administration
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 121 115
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
0.06
(0.01 to 0.10)
0.01
(-0.03 to 0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.173
Comments [Not Specified]
Method ANCOVA
Comments Model terms: treatment, region (US, non-US) and baseline FEV1 as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval 95%
-0.02 to 0.11
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Total Dose of β-agonist Administered Per Patient Over a Period of 2 Hours Following the End of Study Drug Administration
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 144 127
Median (Inter-Quartile Range)
Unit of Measure: mg
1.0
(0.0 to 4.3)
0.6
(0.0 to 3.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Montelukast Intravenous (IV) 5.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.580
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model (Nonparametric) based on Tukey's normalized ranks with terms treatment, region (US, non-US) and baseline FEV1 as covariate
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Montelukast Intravenous (IV) 5.25 mg Placebo
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Montelukast Intravenous (IV) 5.25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Montelukast Intravenous (IV) 5.25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2   2 
Infections and infestations     
Any Infections And Infestations * 1  1/145 (0.69%)  0/131 (0.00%) 
Pneumonia * 1  1/145 (0.69%)  0/131 (0.00%) 
Injury, poisoning and procedural complications     
Any Injury, Poisoning And Procedural Complications * 1  0/145 (0.00%)  1/131 (0.76%) 
Overdose * 1  0/145 (0.00%)  1/131 (0.76%) 
Respiratory, thoracic and mediastinal disorders     
Any Respiratory, Thoracic And Mediastinal Disorders * 1  2/145 (1.38%)  1/131 (0.76%) 
Asthma * 1  0/145 (0.00%)  1/131 (0.76%) 
Asthmatic Crisis * 2  2/145 (1.38%)  0/131 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.1
2
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Montelukast Intravenous (IV) 5.25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   20   21 
Cardiac disorders     
Any Cardiac Disorders * 1  1/145 (0.69%)  0/131 (0.00%) 
Tachycardia * 1  1/145 (0.69%)  0/131 (0.00%) 
Gastrointestinal disorders     
Any Gastrointestinal Disorders * 1  5/145 (3.45%)  6/131 (4.58%) 
Abdominal Pain * 1  0/145 (0.00%)  1/131 (0.76%) 
Abdominal Pain Upper * 1  2/145 (1.38%)  0/131 (0.00%) 
Constipation * 1  0/145 (0.00%)  1/131 (0.76%) 
Diarrhoea * 1  1/145 (0.69%)  1/131 (0.76%) 
Gastrooesophageal Reflux Disease * 1  1/145 (0.69%)  0/131 (0.00%) 
Nausea * 1  1/145 (0.69%)  1/131 (0.76%) 
Vomiting * 1  1/145 (0.69%)  2/131 (1.53%) 
General disorders     
Any General Disorders And Administration Site Conditions * 1  2/145 (1.38%)  1/131 (0.76%) 
Chest Pain * 1  1/145 (0.69%)  0/131 (0.00%) 
Infusion Site Extravasation * 1  0/145 (0.00%)  1/131 (0.76%) 
Infusion Site Pain * 1  1/145 (0.69%)  0/131 (0.00%) 
Infections and infestations     
Any Infections And Infestations * 1  5/145 (3.45%)  5/131 (3.82%) 
Bronchitis Bacterial * 1  1/145 (0.69%)  0/131 (0.00%) 
Gastroenteritis * 1  1/145 (0.69%)  0/131 (0.00%) 
Influenza * 1  0/145 (0.00%)  1/131 (0.76%) 
Nasopharyngitis * 1  1/145 (0.69%)  2/131 (1.53%) 
Pharyngitis * 1  1/145 (0.69%)  0/131 (0.00%) 
Rhinitis * 1  0/145 (0.00%)  1/131 (0.76%) 
Sinusitis * 1  0/145 (0.00%)  2/131 (1.53%) 
Tonsillitis * 1  1/145 (0.69%)  0/131 (0.00%) 
Musculoskeletal and connective tissue disorders     
Any Musculoskeletal And Connective Tissue Disorders * 1  1/145 (0.69%)  1/131 (0.76%) 
Arthralgia * 1  0/145 (0.00%)  1/131 (0.76%) 
Muscle Spasms * 1  1/145 (0.69%)  0/131 (0.00%) 
Nervous system disorders     
Any Nervous System Disorders * 1  6/145 (4.14%)  2/131 (1.53%) 
Dizziness * 1  0/145 (0.00%)  1/131 (0.76%) 
Headache * 1  5/145 (3.45%)  1/131 (0.76%) 
Syncope Vasovagal * 1  1/145 (0.69%)  0/131 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Any Respiratory, Thoracic And Mediastinal Disorders * 1  5/145 (3.45%)  9/131 (6.87%) 
Asthma * 1  4/145 (2.76%)  7/131 (5.34%) 
Atelectasis * 1  1/145 (0.69%)  0/131 (0.00%) 
Rhinitis Allergic * 1  0/145 (0.00%)  2/131 (1.53%) 
Skin and subcutaneous tissue disorders     
Any Skin And Subcutaneous Tissue Disorders * 1  0/145 (0.00%)  2/131 (1.53%) 
Prurigo * 1  0/145 (0.00%)  1/131 (0.76%) 
Pruritus * 1  0/145 (0.00%)  1/131 (0.76%) 
Vascular disorders     
Any Vascular Disorders * 1  0/145 (0.00%)  1/131 (0.76%) 
Diastolic Hypotension * 1  0/145 (0.00%)  1/131 (0.76%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00117338     History of Changes
Other Study ID Numbers: 0476-301
MK0476-301
2005_026
First Submitted: June 30, 2005
First Posted: July 6, 2005
Results First Submitted: March 16, 2009
Results First Posted: August 11, 2009
Last Update Posted: April 6, 2017