Continuous Levalbuterol for Treatment of Status Asthmaticus in Children
Condition: Asthma
MeSH terms: Status Asthmaticus
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Racemic albuterol (R+S albuterol); Levalbuterol (R albuterol)
Intervention type(s): Drug; Drug
Intervention description(s): 20mg/hr continuous racemic albuterol; 10mg/hr continuous nebulized levalbuterol
Other intervention name(s): Xopenex
Intervention MeSH terms: Albuterol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Asthma; Levalbuterol; Albuterol; Children