Albuterol Versus Xopenex in Treatment of Acute Asthma in the Emergency Department (ED)
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine in a large, double-blind, randomized, prospective
      pediatric clinical trial whether the use of continuous levalbuterol (Xopenex) in addition to
      standard emergency department treatment for acute asthma exacerbations will improve the
      Forced Expiratory Volume in 1 sec (FEV 1) compared to the use of continuous racemic
      albuterol. The secondary objective is to correlate clinical (hospitalization rates and
      clinical asthma scores) with plasma levels of (S)-albuterol.
    

Detailed description: 
      Children between the ages of 6 and 17 years inclusive who have a history of asthma are
      eligible for enrollment if they present to the pediatric emergency department with a moderate
      to severe acute asthma exacerbation. All eligible children will be enrolled whenever there
      are study personnel available after obtaining informed written consent. Children less than 6
      years of age will not be enrolled as levalbuterol has only been approved in children 6 years
      of age and greater. Children will also be excluded if their Forced Expiratory Volume in 1 sec
      (FEV 1) is > 70% predicted (see below); they have a history of a chronic lung disease (e.g.
      cystic fibrosis), noncorrected congenital heart disease, suspected intrathoracic foreign
      body, need immediate resuscitation or are pregnant.

      Eligible patients will be identified by research assistants and the attending ED physician
      will be notified. The attending ED physician will make the final decision regarding severity
      based on their physical exam and spirometry (FEV 1) results. The FEV 1 value will be recorded
      and calculated as a percentage of their predicted based on standardized height and weight
      charts. All spirometry will be performed by licensed respiratory therapists or research
      assistants trained in the use of the spirometer. An FEV 1 of 50% to 70% predicted will be
      considered a moderate exacerbation and if less than 50% predicted, severe.

      As the children being enrolled are having significant asthma exacerbations there will be no
      delay in their treatment. If the consent process can not be carried within the first 15
      minutes upon arrival to the ED they will receive a standard dose of albuterol as per our
      standing ED orders.

      A computer generated table of random numbers will be used to assign children to treatment
      group. A locked area in the ED will contain numbered plastic bags each containing either 15
      mg of racemic albuterol or 7.5 mg of levalbuterol. Since we are only enrolling children ≥ 6
      years of age they should all weigh > 20 kg and therefore will receive 7.5 mg of racemic
      albuterol (0.5%, 2.5mg/0.5 ml Nephron Pharmaceuticals) in normal saline (total volume = 20
      ml) nebulized over one hour if assigned to the albuterol group (i.e. the equivalent of 2.5 mg
      every 20 minutes for 3 doses). If they are between 6 and 11 years of age they will receive
      1.89 mg levalbuterol and if ≥ 12 years of age 3.75 mg of levalbuterol in the same volume of
      normal saline. This would be the equivalent of giving 3 treatments every 20 minutes for one
      hour. Both study medications will be identical in odor and appearance. All children will
      receive 2 mg/kg of methylprednisolone up to a maximum dose of 60 mg orally within the first
      20 minutes of treatment. All children will also receive two unit doses of ipratropium bromide
      (1000 mcg) in the first hour of nebulization therapy as this is standard of care.

      Spirometry will be performed at baseline and after each hour of bronchodilator treatment
      until the child is discharged home or is admitted to an in-patient unit. Patient disposition
      from the ED depends on their response to treatment. The ultimate decision to admit or
      discharge will be at the attendings discretion. However, if the child is able to perform good
      loops on spirometry then FEV1 may be used to guide the decision. An FEV 1 ≥ 70% predicted
      will likely mean discharge to home with appropriate instructions. Children will be observed
      for 60 minutes after their last bronchodilator treatment to ensure that they maintain their
      response. Children will be admitted to the PICU if their FEV 1 < 50% or if they require
      inhaled bronchodilators more than hourly. If the child's FEV 1 is ≥ 50% but < 70% or if they
      are still experiencing moderate symptoms they are likely to be admitted to the floor but
      further treatment in the ED may allow sufficient improvement for discharge. If after a
      further treatment period of one hour their FEV1 is > 70% they will be discharged home. If it
      is < 70% they will be admitted. Once disposition has been decided the study is concluded for
      that patient except for telephone follow-up if the child was discharged home.

      All children discharged home will be called 30 days after their ED assessment. This call will
      determine if the child had any further unscheduled ED or office visits for the same asthma
      exacerbation.

      Data to be collected include the child's age, weight, height, gender, ethnicity, medication
      use at home, asthma history, asthma scores, peak flows, disposition from ED, adverse effects,
      and serum levels of the albuterol isomers (see data collection sheet attached).

      Blood will be drawn at baseline. The serum level for albuterol enantiomers requires 7 ml of
      blood and will only be drawn once. Children can elect to be in just the RCT of the two
      medications or to take part in both parts of the study. Blood samples will be sent to the
      lab, spun down and frozen. The samples will be stored there until the study is completed and
      then shipped to an outside lab for measurement of plasma levels of (S) and (R) albuterol.
      These plasma levels will only be reviewed after patient disposition has already been decided
      as they are not clinically relevant to their acute management at this time.

      There will be dedicated research personal in the ED 16 hours a day for the sole purpose of
      identifying study candidates and ensuring all procedures are followed according to the
      protocol. This is to ensure continuity through the study process including placement of the
      consent in the medical record. Since spirometry is an objective test it also allows for shift
      changes without the need to worry about a different individual measuring the FEV1. Despite
      this all ED staff (physicians, fellows, nurses, technicians) will be informed and educated on
      the purpose, protocol and procedures to be used in the study at regularly scheduled staff
      meetings.
    

Intervention name(s): xopenex
Intervention type(s): Drug
Intervention description(s): will receive xopenex rather than albuterol to treat acute exacerbation
Other intervention name(s): levalbuterol
Intervention MeSH terms: Albuterol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: child; emergency department