A Comparison of Levalbuterol Plus Ipratropium With Levalbuterol Alone in the Treatment of Acute Asthma Exacerbation
A Comparison of Levalbuterol Plus Ipratropium With Levalbuterol Alone in the Treatment of Acute Asthma Exacerbation
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.
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