Continuous Levalbuterol for Treatment of Status Asthmaticus in Children

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

• 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 ]
  

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.