Asthma
Conditions
Keywords
Asthma, Bronchodilators, Levalbuterol, Ipratropium
Brief summary
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.
Detailed description
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.
Interventions
DRUGipratropium
0.5 mg of ipratropium added to 1.25 mg levalbuterol given every 20 minutes for 3 doses
Sponsors
Sumitomo Pharma America, Inc.
MetroHealth Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* 18-45 years of age * history of asthma * FEV1 \> 50% of predicted for their height, age, gender and race upon presentation to the ED * no other cause of wheezing or shortness of breath except for asthma as determined by the Investigator * no history of glaucoma * no Ipratropium or other anticholinergics within 6 hours of study
Exclusion criteria
* subjects who, in the investigator's opinion, have life-threatening asthma requiring emergent intervention precluding the ability to complete the treatments during the treatment period * based upon history or physical exam in the ED orClinic, subjects with known or suspected cause of pulmonary symptoms other than asthma, such as COPD, CHF, pneumonia, pulmonary embolism, or angioedema * subject with a known sensitivity to levalbuterol or racemic albuterol * known 20 pack year smoker * use of ipratropium 6 hours prior to presenting to the ED * subject who may be pregnant or is pregnant es evidenced by pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bronchodilation | 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. | 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. |
| Change in FEV-1 % Predicted Over Time | 60 minutes | 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 |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 74 |
| 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 | 67 |
| Total | 141 |
Baseline characteristics
| Characteristic | Levalbuterol Plus Ipratropium | Levalbuterol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 67 Participants | 74 Participants | 141 Participants |
| Age, Continuous | 30.3 years | 31.1 years | 30.6 years |
| Region of Enrollment United States | 67 Participants | 74 Participants | 141 Participants |
| Sex: Female, Male Female | 36 Participants | 54 Participants | 90 Participants |
| Sex: Female, Male Male | 31 Participants | 20 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 67 |
| other Total, other adverse events | 0 / 74 | 0 / 67 |
| serious Total, serious adverse events | 0 / 74 | 0 / 67 |
Outcome results
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
Time frame: 60 minutes
Population: Overall Number of Participants Analyzed 141
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levalbuterol | Change in FEV-1 % Predicted Over Time | 45 percentage of FEV-1 predicted |
| Levalbuterol Plus Ipratropium | Change in FEV-1 % Predicted Over Time | 47 percentage of FEV-1 predicted |
Comparison: Data were analyzed using STATA 10 SE.Categorical variables were described using frequencies and relative frequencies. Distribution of continuous variables were evaluated for normality using the Shapiro-Walk test and graphically using histograms and box plots. Because most data were non-parametric, they were described using the median and 25th and 75th percentiles (interquartile range) and then compared using Wilcoxon rank sum test.p-value: <0.05Wilcoxon (Mann-Whitney)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Levalbuterol | Number of Participants With Bronchodilation | 74 Participants |
| Levalbuterol Plus Ipratropium | Number of Participants With Bronchodilation | 67 Participants |