Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

Study Overview
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Brief Summary
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This study will use a randomized, double-blind, controlled trial design in order to assess the safety and efficacy of levalbuterol (LEV) compared to racemic albuterol (RAC) when delivered continuously in a high-dose regimen for children with severe exacerbations of asthma. Primary hypothesis Children with severe asthma receiving continuous levalbuterol will have a shorter duration of continuous therapy as compared to racemic albuterol. Secondary hypotheses Children receiving continuous levalbuterol will have improved lung function measured by forced expiratory volume at 1 second (FEV1) as compared to racemic albuterol. Children receiving continuous levalbuterol will have improved clinical asthma score as compared to racemic albuterol.

Detailed Description
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High-dose nebulized albuterol is standard therapy for severe asthma exacerbations at The Children's Hospital of Philadelphia (CHOP) and other tertiary care pediatric hospitals throughout the United States. For the most severe exacerbations, albuterol is provided continuously at high doses until improvement is observed. This regimen has been standardized in a treatment protocol that has been used at CHOP for more than 5 years. Recently, levalbuterol (LEV), the purified active (R)-enantiomer of albuterol, has been approved for use in acute asthma. Preliminary evidence suggests that LEV may improve pulmonary function and clinical outcomes in children with asthma based on studies using standard dosing regimens. Laboratory and clinical evidence suggest that the (S)-enantiomer of albuterol may have detrimental effects that contribute to poor response to racemic albuterol (RAC). Limited data exist about the efficacy of LEV in high-dose regimens. This study will use a randomized, double-blind, controlled trial design in order to assess the safety and efficacy of LEV compared to RAC when delivered continuously in a high-dose regimen for severe exacerbations of asthma. Children treated for asthma exacerbations in the CHOP emergency department (ED) will be eligible for study enrollment. Those that meet enrollment criteria will be randomized to receive either high dose RAC according to the standard asthma care protocol or equivalent dosing of LEV. Approximately 128 patients with 64 in each arm of the study will be enrolled. An interim safety analysis will be conducted after the first 40 patients are enrolled. This study should be completed in six to nine months. The primary outcome will be duration of continuous therapy. Secondary outcomes will include improvement of clinical asthma score and change in forced expiratory volume in one second (FEV1). In addition, (R)-albuterol and (S)-albuterol levels will be measured at study entry and at 6-hour intervals in the first 40 patients enrolled. These values will be used to determine prior RAC exposure and to determine serum levels of (R) and (S) albuterol during continuous therapy.

Official Title
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Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

Conditions
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Asthma

Intervention / Treatment
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* Drug: Racemic albuterol (R+S albuterol)
* Drug: Levalbuterol (R albuterol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6-18 years of age Diagnosis of asthma with two previous visits to emergency department (ED) or primary care provider for asthma care Clinical decision by ED attending physician to begin continuous albuterol after standardized initial ED treatment. Exclusion Criteria: Clinical decision to begin continuous intravenous beta-agonist infusion (e.g. terbutaline) Clinical decision to admit to the Pediatric Intensive Care Unit Drug allergy or other contraindication to RAC or LEV Other concurrent disease such as sickle cell disease, cystic fibrosis, or cardiac disease Pregnancy Prior enrollment in the study

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 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: 1<br>Nebulized levalbuterol 10mg/hr given continuously | Drug: Levalbuterol (R albuterol)<br>* 10mg/hr continuous nebulized levalbuterol<br>* Other names: Xopenex;|
| Active Comparator: 2<br>Racemic albuterol 20mg/hr given continuously | Drug: Racemic albuterol (R+S albuterol)<br>* 20mg/hr continuous racemic albuterol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Continuous Therapy | standard intention to treat (ITT) analysis | During hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pediatric Asthma Severity Score | Change in Pediatric Asthma Severity Score. Range 0 (best) - 6 (worst) Score at each time point is calculated by adding 3 elements: Wheeze (0= None/Mild, 1=Moderate, 2=Severe) Prolonged expiration (0= None/Mild, 1=Moderate, 2=Severe) Work of breathing (0= None/Mild, 1=Moderate, 2=Severe) | After 12 hours of continuous nebulization | 
| Heart Rate |  | After 12 hours of continuous nebulization | 
| Serum Potassium Levels |  | After 12 hours of continuous nebulization | 
| Serum Albuterol S Isomer Levels |  | After 6 hours of continuous albuterol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Levalbuterol, Albuterol, Children