A Pilot Study to Determine the Most Effective Dose of Arformoterol for Treating Acute Asthmatic Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine the best dose of nebulized arformoterol, a quick onset but long acting beta agonist, for use in treating acute bronchospasm in asthmatics presenting to the the Emergency Department. Also this study will evaluate the side effect and safety profile of arformoterol when used in this situation.

Detailed Description
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Acute bronchospasm associated with exacerbations of asthma is a common problem. Currently the mainstay of treatment is inhalation albuterol, either levalbuterol or racemic mixture, in repetitive fashion depending on the resolution of the airways obstruction. Formoterol is a long-acting (>12 hours) selective beta2-agonist that has a very rapid onset of bronchodilatation (<3 minutes and thus similar to that produced by albuterol). Patients with acute bronchospasm could benefit from the prn use of formoterol as they would receive acute relief of their symptoms and this would last for a prolonged time period. Additionally formoterol has been reported to be 28-109 times as potent as albuterol and safe at doses of 54ug in healthy subjects and asthmatics. Racemic formoterol structurally has 2 chiral centers and thus is composed of 4 enantiomers. The RR form (or arformoterol) is the active bronchodilator and it is not clear what the physiologic actions of the other 3 enantiomers are. This study is the first to evaluate nebulized arformoterol solution for therapy of acute asthmatics presenting to the Emergency Department.

Official Title
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A Pilot Study to Determine the Most Effective Dose of Arformoterol for Treating Acute Asthmatic Patients Presenting to the Emergency Department and to Evaluate Its Side Effect and Safety Profile When Used in This Clinical Situation.

Conditions
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Acute Asthma

Intervention / Treatment
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* Drug: arformoterol (RR formoterol)
* Drug: placebo
* Drug: levalbuterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent FEV1 between 20 and 60% predicted after having received 5 mg of albuterol and 0.5 mg of atrovent as nebulized standard of care therapy Male or female between the ages of 18 and 45 Asthma diagnosed by a physician and present for at least 6 months oxygen saturation greater or equal to 90% on room air Non smoker or < 10 pack-year history No other cause for wheezing/sob as determined by the treating physician Exclusion Criteria: Clinical evidence or history of hepatic, renal, cardiovascular, GI, endocrine, metabolic or CNS disease which might interfere with the conduct of the study Acute respiratory failure or other significant pathology of the pulmonary system Female subjects who are pregnant or lactating Currently receiving therapy for a psychiatric disorder Subjects with a known sensitivity to formoterol (racemic or RR) or albuterol (racemic or lev) History of hospitalization for asthma within 2 months or treatment for acute asthma in an ED within 2 weeks of study entry Past or current use of disallowed medications Participation in an investigational study within 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arformoterol 3 doses<br> | Drug: arformoterol (RR formoterol)<br>* Group 1 will receive nebulized arformoterol 15 ug every 20 minutes for 3 doses. Group 2 will receive nebulized arformoterol 15 ug first dose and then placebo every 20 minutes for 2 doses.<br>* Other names: Brovana;|
| Experimental: Arformoterol 1 dose, placebo 2 doses<br> | Drug: arformoterol (RR formoterol)<br>* Group 1 will receive nebulized arformoterol 15 ug every 20 minutes for 3 doses. Group 2 will receive nebulized arformoterol 15 ug first dose and then placebo every 20 minutes for 2 doses.<br>* Other names: Brovana;Drug: placebo<br>* Group 2 will receive nebulized arformoterol 15 ug first dose and then placebo every 20 minutes for 2 doses.<br>|
| Active Comparator: Levalbuterol 3 doses<br> | Drug: levalbuterol<br>* Group 3 will receive nebulized levalbuterol 1.25 mg every 20 minutes for 3 doses.<br>* Other names: Xopenex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Averaged Mean Percent Change From Baseline FEV1 and PEFR (Percent Predicted and Absolute) After the 3 Doses of Study Drug |  | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Most Effective Dose of Inhalation Arformoterol for Treating Acute Bronchospasm in Asthmatics by Evaluating the Averaged Mean Percent Change From Baseline % Predicted FEV1 After 3 Doses of Study Medication in Each of the 3 Groups | The study was terminated early and therefore secondary outcome measures were not obtained. | 1 hour | 
| Number of Participants Treated With Arformoteral in Acute Asthma Exacerbation as a Measure of Safety and Tolerability. | The study was terminated early and therefore secondary outcome measures were not obtained. | 5 hours | 
| The Mean Percent Change From Baseline in the FEV1 and PEFR (Absolute and Percent Predicted) Following Each Dose of Study Drug |  | 1 hour | 
| The Mean Change From Baseline in the FEV1 and PEFR (Absolute and Percent Predicted) Following Each Dose of Study Drug | The study was terminated early and therefore secondary outcome measures were not obtained. | 1 hour | 
| The Peak Change (Liters) and Peak Percent Change From Baseline in the FEV1 and PEFR (Absolute and Percent Predicted) Following Each Dose of Study Drug |  | 1 hour | 
| The Time to Onset of a 15% Improvement in FEV1 for Each Dose (Individual and Cumulative) and Total Dose of Study Medication to Reach This |  | 5 hour | 
| The Time Required to Achieve a FEV1 and PEFR > 60% Predicted for Each Dose (Individual and Cumulative) |  | 5 hours | 
| Percent of Responders (Defined as Those Discharged Following Treatment Who Did Not Require Additional Therapy in the ED) | The 2 subjects enrolled were both discharged home after study protocol completion, with no further treatment required in the ED setting. | 5 hours | 
| Percent of Patients in Each Group Requiring Additional Therapies After the First Hour of Study Drug Treatments | 2 subjects were enrolled. Neither required additional asthma treatment after the 1st hour of study drug teatments. | 5 hours | 
| All of the Primary and Secondary Endpoints Partitioned by the Presenting PFT in Quartiles and the Presenting S Albuterol Levels in Quartiles |  | 5 hours | 
| Pharmacokinetics of Arformoterol in This Clinical Setting |  | 5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute asthma, Arformoterol, Long acting beta agonists