Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

• ClinicalTrials.gov Identifier: NCT00124176
• Recruitment Status: Completed
• First Posted: July 27, 2005
• Results First Posted: March 14, 2013
• Last Update Posted: March 14, 2013
• Sponsor: Children's Hospital of Philadelphia
• Collaborator: Sunovion
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Racemic albuterol (R+S albuterol); Drug: Levalbuterol (R albuterol)	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Continuous Levalbuterol for Treatment of Status Asthmaticus in Children
• Study Start Date: April 2004
• Actual Primary Completion Date: February 2006
• Actual Study Completion Date: February 2006

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Duration of Continuous Therapy [ Time Frame: During hospitalization ]
   standard intention to treat (ITT) analysis

Secondary Outcome Measures :

1. 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)

2. Heart Rate [ Time Frame: After 12 hours of continuous nebulization ]
3. Serum Potassium Levels [ Time Frame: After 12 hours of continuous nebulization ]
4. Serum Albuterol S Isomer Levels [ Time Frame: After 6 hours of continuous albuterol ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT00124176
• Other Study ID Numbers: #2004-12-4130
• First Posted: July 27, 2005
• Results First Posted: March 14, 2013
• Last Update Posted: March 14, 2013
• Last Verified: December 2012

Keywords provided by Children's Hospital of Philadelphia:

Asthma; Levalbuterol; Albuterol; Children

Additional relevant MeSH terms:

Status Asthmaticus; Asthma; Bronchial Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action