Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

NCT ID: NCT00124176

Last Updated: 2013-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30
• Study Completion Date: 2006-02-28

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Nebulized levalbuterol 10mg/hr given continuously

Group Type: EXPERIMENTAL

Levalbuterol (R albuterol)

Intervention Type: DRUG

10mg/hr continuous nebulized levalbuterol

2

Racemic albuterol 20mg/hr given continuously

Group Type: ACTIVE_COMPARATOR

Racemic albuterol (R+S albuterol)

Intervention Type: DRUG

20mg/hr continuous racemic albuterol

Interventions

Racemic albuterol (R+S albuterol)

20mg/hr continuous racemic albuterol

Intervention Type: DRUG

Levalbuterol (R albuterol)

10mg/hr continuous nebulized levalbuterol

Intervention Type: DRUG

Other Intervention Names

Xopenex

Eligibility Criteria

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph J Zorc, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

#2004-12-4130

Identifier Type: -

Identifier Source: org_study_id