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| Name | Class |
|---|---|
| Sumitomo Pharma America, Inc. | INDUSTRY |
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This is a double blind, controlled clinical trail testing whether three doses of 1.25 mg of nebulized levalbuterol in combination with three doses of 0.5mg of nebulized ipratropium will lead to greater bronchodilation than that achieved by three doses of nebulized 1.25 mg of levalbuterol alone every 20 minutes.
The primary hypothesis of this study is that three doses of 1.25 mg of nebulized levalbuterol in combination with three doses of 0.5mg of nebulized ipratropium will lead to greater bronchodilation than that achieved by three doses of nebulized 1.25 mg of levalbuterol alone every 20 minutes. The secondary hypothesis is that the treatment combination of levalbuterol and ipratropium will lead to fewer hospitalizations than levalbuterol alone in patients with acute asthma exacerbation. Other secondary objectives include (1) evaluating the relationship between baseline (S)- albuterol levels and (R)- albuterol levels on presentation and FEV1, (2) the relationship between baseline (S)- albuterol levels and (R)- albuterol levels on presentation and change in FEV1,(3) time to event analysis for an improvement of 15%, 20%, 30%, 40%, and 50% in FEV1 from initial presentation value, (4) analysis of FEV1 at discharge.
Patients will then receive, in a randomized double-blinded fashion, levalbuterol, 1.25mg every 20 minutes for a total of 3 aerosolized doses combined with ipratropium, 0.5mg every 20 minutes for a total of 3 aerosolized doses. The medication will be premixed by the pharmacy in a total of 3 ml of normal saline and the nebulizer will be driven with oxygen at 6 liters per minute. A second plasma sample for analysis of albuterol isomers will be drawn within a fifteen minute window following the third aerosol treatment. Spirometry will be repeated again at 30 and 60 minutes after the third aerosol treatment (Figure 1). All patients will receive prednisone, 60mg orally immediately after their first dose of aerosolized medications, unless contraindications to prednisone administration are present. Patients will not receive any other medications during the time course of the study. Vital signs and pulse oximetry will be repeated prior to each nebulized treatment and again 30 minutes after the third nebulized treatment.
The study will terminate 60 minutes after the third aerosol administration. At that point, any further therapy will be at the discretion of the treating physician. Patients will be questioned about the occurrence of any side effects from levalbuterol treatment including palpitations, anxiety, nausea, vomiting or headache. Patients will also be questioned about the occurrence of any side effects from ipratropium, including dry mouth, dry eyes, and urinary retention. Patients will be withdrawn from the study at any point these side effects become intolerable to the patient or any time the patient so desires. Patients will also be withdrawn if they develop palpitations and have an ECG that demonstrates ventricular or supraventricular tachycardia.
.Patients will be called 14 days after their ED visit to assess relapse or recurrence of acute asthma exacerbation. In addition, a chart review will be performed to assess relapse or recurrence of acute asthma exacerbation, as well as determine hospital length of stay in those patients who required admission after the initial visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Levalbuterol | Active Comparator | levalbuterol 1.25 mg every 20 minutes for 3 doses plus placebo (saline) |
|
| Levalbuterol plus ipratropium | Experimental | ipratropium 0.5 mg nebulized every 20 minutes for 3 doses added to levalbuterol 1.25 mg every 20 minutes for 3 doses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ipratropium | Drug | 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Bronchodilation | Measure FEV-1 in participants immediately prior to treatment and 60 minutes after final treatment to determine improvement in bronchodilation after 1.25mg nebulized levalbuterol + 0.5mg nebulized ipratropium administered every 20 minutes for a total of 3 doses versus bronchodilation after 1.25mg nebulized levalbuterol administered every 20 minutes for a total of 3 doses. FEV-1 measurements were obtained using a hand held spirometer. A difference in 12% of median FEV-1 measures between the two groups was considered clinically significant. Patients were called 14 days after their ED visit to assess relapse or recurrence of acute asthma exacerbation. In addition, a chart review was performed to assess relapse or recurrence of acute asthma exacerbation, as well as determine hospital length of stay in those patients who required admission after the initial visit. | FEV-1 measured Immediately before treatment dose 1 & 60 minutes after completion of treatment dose 3. Assessment of relapse or recurrence were determined at day 14 after the ED visit. |
| Change in FEV-1 % Predicted Over Time | Primary Outcome- the difference in FEV-1at 60 minutes between participants who received Levalbuterol 1.25 mg x 3 vs participants who received Levalbuterol 1.25 mg x3 + Ipratropium 0.5 mg x3 | 60 minutes |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rita K Cydulkla, MD | MetroHealth Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MetroHealth Medical Center | Cleveland | Ohio | 44109 | United States |
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Adult patients between the ages if 18 and 45 years presenting to the emergency department with acute asthma. They were enrolled by one of the study nurses. Patients were eligible to enroll if their FEV-1 was less than 50% predicted on arrival. Enrollment occurred between December 2005 and December 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Levalbuterol | levalbuterol 1.25 mg every 20 minutes for 3 doses plus placebo (saline) ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses |
| FG001 | Levalbuterol Plus Ipratropium | ipratropium 0.5 mg nebulized every 20 minutes for 3 doses added to levalbuterol 1.25 mg every 20 minutes for 3 doses ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Levalbuterol | levalbuterol 1.25 mg every 20 minutes for 3 doses plus placebo (saline) ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses |
| BG001 | Levalbuterol Plus Ipratropium |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Bronchodilation | Measure FEV-1 in participants immediately prior to treatment and 60 minutes after final treatment to determine improvement in bronchodilation after 1.25mg nebulized levalbuterol + 0.5mg nebulized ipratropium administered every 20 minutes for a total of 3 doses versus bronchodilation after 1.25mg nebulized levalbuterol administered every 20 minutes for a total of 3 doses. FEV-1 measurements were obtained using a hand held spirometer. A difference in 12% of median FEV-1 measures between the two groups was considered clinically significant. Patients were called 14 days after their ED visit to assess relapse or recurrence of acute asthma exacerbation. In addition, a chart review was performed to assess relapse or recurrence of acute asthma exacerbation, as well as determine hospital length of stay in those patients who required admission after the initial visit. | Posted | Count of Participants | Participants | FEV-1 measured Immediately before treatment dose 1 & 60 minutes after completion of treatment dose 3. Assessment of relapse or recurrence were determined at day 14 after the ED visit. |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Levalbuterol | levalbuterol 1.25 mg every 20 minutes for 3 doses plus placebo (saline) ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rita Cydulka | MetroHealth Medical Center | 216-778-7800 | rcydulka@gmail.com |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D009241 | Ipratropium |
| ID | Term |
|---|---|
| D001286 | Atropine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
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ipratropium 0.5 mg nebulized every 20 minutes for 3 doses added to levalbuterol 1.25 mg every 20 minutes for 3 doses
ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG000 | Levalbuterol | levalbuterol 1.25 mg every 20 minutes for 3 doses plus placebo (saline) |
| OG001 | Levalbuterol Plus Ipratropium | ipratropium 0.5 mg nebulized every 20 minutes for 3 doses added to levalbuterol 1.25 mg every 20 minutes for 3 doses ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses |
|
|
| Primary | Change in FEV-1 % Predicted Over Time | Primary Outcome- the difference in FEV-1at 60 minutes between participants who received Levalbuterol 1.25 mg x 3 vs participants who received Levalbuterol 1.25 mg x3 + Ipratropium 0.5 mg x3 | Overall Number of Participants Analyzed 141 | Posted | Median | Inter-Quartile Range | percentage of FEV-1 predicted | 60 minutes |
|
|
|
|
| 0 |
| 74 |
| 0 |
| 74 |
| 0 |
| 74 |
| EG001 | Levalbuterol Plus Ipratropium | ipratropium 0.5 mg nebulized every 20 minutes for 3 doses added to levalbuterol 1.25 mg every 20 minutes for 3 doses ipratropium: 0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses | 0 | 67 | 0 | 67 | 0 | 67 |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D009930 |
| Organic Chemicals |
| D001533 | Belladonna Alkaloids |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
This study was designed to detect an absolute difference of 12 % in change of FEV-1percent predicted, with a standard deviation of 25% based on data provided to us from previous studies conducted by Sepracor. Based on this assumption, we sought to enter 76 patients in each group to have an 80% power to detect a 12 % absolute difference in charge of FEV-1 percent predicted over time at an alpha of 0.05. This accounted for a potential 10% dropout rate after randomization. |