Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

This study has been completed.
Sponsor:
Collaborator:
Sunovion
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00124176
First received: July 25, 2005
Last updated: February 12, 2013
Last verified: December 2012
  Purpose

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.

Condition Intervention Phase
Asthma
Drug: Racemic albuterol (R+S albuterol)
Drug: Levalbuterol (R albuterol)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Duration of Continuous Therapy [ Time Frame: During hospitalization ] [ Designated as safety issue: No ]
    standard intention to treat (ITT) analysis


Secondary Outcome Measures:
  • Change in Pediatric Asthma Severity Score [ Time Frame: After 12 hours of continuous nebulization ] [ Designated as safety issue: No ]

    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 [ Time Frame: After 12 hours of continuous nebulization ] [ Designated as safety issue: No ]
  • Serum Potassium Levels [ Time Frame: After 12 hours of continuous nebulization ] [ Designated as safety issue: No ]
  • Serum Albuterol S Isomer Levels [ Time Frame: After 6 hours of continuous albuterol ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: April 2004
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Nebulized levalbuterol 10mg/hr given continuously
Drug: Levalbuterol (R albuterol)
10mg/hr continuous nebulized levalbuterol
Other Name: Xopenex
Active Comparator: 2
Racemic albuterol 20mg/hr given continuously
Drug: Racemic albuterol (R+S albuterol)
20mg/hr continuous 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.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00124176

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Sunovion
Investigators
Principal Investigator: Joseph J Zorc, MD Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00124176     History of Changes
Other Study ID Numbers: #2004-12-4130
Study First Received: July 25, 2005
Results First Received: July 14, 2010
Last Updated: February 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Asthma
Levalbuterol
Albuterol
Children

Additional relevant MeSH terms:
Asthma
Status Asthmaticus
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014