Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

Phase 4

Completed

• Conditions: Asthma
• Interventions: Drug: Levalbuterol (R albuterol); Drug: Racemic albuterol (R+S albuterol)

• Registration Number: NCT00124176
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

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

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.

Study Timeline

• Study Start: 2004-04
• Study First Submitted: 2005-07-25
• Study First Submitted QC: 2005-07-26
• Study First Posted: 2005-07-27
• Primary Completion: 2006-02
• Study Completion: 2006-02
• Results First Submitted: 2010-07-14
• Status Verified: 2012-12
• Results First Submitted QC: 2013-02-12
• Last Update Submitted: 2013-02-12
• Results First Posted: 2013-03-14
• Last Update Posted: 2013-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 81

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Levalbuterol (R albuterol)	Nebulized levalbuterol 10mg/hr given continuously
2	Racemic albuterol (R+S albuterol)	Racemic albuterol 20mg/hr given continuously

Primary Outcome Measures

Name	Time	Method
Duration of Continuous Therapy	During hospitalization	standard intention to treat (ITT) analysis

Secondary Outcome Measures

Name	Time	Method
Change in Pediatric Asthma Severity Score	After 12 hours of continuous nebulization	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)
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

Trial Locations

Locations (1)

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States