Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

February 12, 2013 updated by: Children's Hospital of Philadelphia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Nebulized levalbuterol 10mg/hr given continuously
Drug: Levalbuterol (R albuterol)
10mg/hr continuous nebulized levalbuterol
Other Names:
  • Xopenex
Active Comparator: 2
Racemic albuterol 20mg/hr given continuously
Drug: Racemic albuterol (R+S albuterol)
20mg/hr continuous racemic albuterol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Pediatric Asthma Severity Score
Time Frame: 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)
After 12 hours of continuous nebulization
Heart Rate
Time Frame: After 12 hours of continuous nebulization
After 12 hours of continuous nebulization
Serum Potassium Levels
Time Frame: After 12 hours of continuous nebulization
After 12 hours of continuous nebulization
Serum Albuterol S Isomer Levels
Time Frame: After 6 hours of continuous albuterol
After 6 hours of continuous albuterol

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Philadelphia

Collaborators

Sunovion

Investigators

  • Principal Investigator: Joseph J Zorc, MD, Children's Hospital of Philadelphia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Primary Completion (Actual)

February 1, 2006

Study Completion (Actual)

February 1, 2006

Study Registration Dates

First Submitted

July 25, 2005

First Submitted That Met QC Criteria

July 26, 2005

First Posted (Estimate)

July 27, 2005

Study Record Updates

Last Update Posted (Estimate)

March 14, 2013

Last Update Submitted That Met QC Criteria

February 12, 2013

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #2004-12-4130

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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