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Completed

NCT Number: NCT01323010

Efficacy and Safety of Increasing Doses of Inhaled Albuterol in Children With Acute Wheezing Episodes

Metered dose inhalers with spacers are devices capable of providing higher rates of lung deposition of drugs such as beta agonists when compared to conventional nebulizers, but there is no consensus about the optimal dose when this is the device of choice and there is evidence that younger children need proportionally higher doses of albuterol (in μg/kg) when compared to older children. Other factors that may interfere with response to albuterol treatment include the genetics of the beta adrenergic receptor (ADRβ2) and infectious etiology of the wheezing attack. This study will assess the effectiveness of a dose regimen that prioritizes higher doses of albuterol, with doses in μg/kg higher for younger children. Security of this new dosing regimen will be assessed by monitoring clinical side effects and serum levels of albuterol, but the investigators will also examine the presence of 12 different respiratory viruses in these patients and evaluate the influence of ADRβ2 receptor genetics in the response to albuterol. The primary outcome measure will be the need for hospitalization. Secondary outcomes will include a change in clinical score, respiratory rate and forced expiratory volume in the first second, the need for additional treatments and length of stay in the emergency room for those not hospitalized.

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Key information

Conditions

Asthma Bronchial Diseases Children Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

2 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Instituto da Crianca HCFMUSP

São Paulo, 05403-010, Brazil

About this study

This is a prospective, randomized, double blinded, controlled study. The patients will be randomly assigned to one of the treatment groups (experimental or control groups).

The patients will be assessed 1 hour later and every 30 minutes thereafter until discharge. Following 4 hours in the emergency room, any patient who do not meet the discharge criteria (PRAM score ≤ 3 and SpO2 ≥ 92%) will be admitted to the hospital. Each patient's attending physician will determine the need for additional therapies following the first hour.

Identification of respiratory viruses in the nasal lavage samples wil be performed using the CLART PneumoVir® kit.

Albuterol plasmatic levels will be analyzed via HPLC (High Performance Liquid Chromatography).

To genotype the ADBR2 receptor (blood samples), the gene regions encompassing the Arg16Gly, Gln27Glu, and Arg19Cys Thr164Ile polymorphisms will be amplified via PCR. The resultant amplimers were then sequenced.

A sample of 124 patients (62 in each group) was calculated to provide an 80% power with which to detect a significant difference of at least 30 minutes in the lengths of stay between the groups. The chi-square test will be used to compare hospital admission rates and tremor rates. For all other outcomes, t-tests for mean comparisons (variables with a normal distribution), a Mann Whitney test (nonparametric data) and ANOVA with repeated measures will be used.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Aged 2 to 18 years;
  • History of two or more previous episodes of wheezing treated with bronchodilators in the last year;
  • Wheezing attacks characterized by coughing, difficulty breathing and auscultation of expiratory wheezing or prolonged expiration;
  • Intensity of wheezing attacks defined by PRAM score as moderate or severe (PRAM ≥ 5).

Exclusion criteria

  • Pre-existing chronic diseases such as bronchopulmonary dysplasia, cystic fibrosis, bronchiolitis obliterans or other chronic pulmonary or cardiovascular disease;
  • Initial clinical status indicating immediate ventilatory support, need for subcutaneous or intravenous bronchodilators;
  • Decreased level of consciousness;
  • Using a β-agonist in the four hours prior to arrival.
  • Use of corticosteroids in the last 24h.

Treatment and study plan

Albuterol - Experimental

Drug

The Experimental group will receive higher doses of albuterol in the first hour: 900 mcg (up to 15 kg), 1200 mcg (> 15 to 20 kg), 1500 mcg (> 20 to 25 kg) and 1800 mcg (> 25 kg).

Other names: Ventolin

Albuterol - Control

Drug

The Control group will receive the following doses of albuterol in the first hour 600 mcg (up to 25 kg) or 1200 mcg (> 25 kg)

Other names: Ventolin

Primary outcomes

  1. Hospital Admission

    Time frame: Starting at 4 hours post-treatment

    Hospital admission was defined as the need to stay in the emergency room for more than 4 hours, due to the failure to meet the discharge criteria (PRAM score ≤ 3 and pulse oximetry, ≥ 92%)

Secondary outcomes

  1. Forced Expiratory Volume in the First Second

    Time frame: One hour post-treatment in comparison with baseline

    Change in FEV1 one hour post-treatment in comparison with baseline. Spirometry was performed only in subjects older than 6 years and who could perform the maneuver properly.

  2. Change in PRAM Score After One Hour

    Time frame: One hour post-treatment

    Change in the Pediatric Respiratory Assessment Measure (PRAM) score one hour post-treatment in comparison with baseline.

    The PRAM score is used to assess the severity of asthma attacks, it ranges from 0 to 15, and the higher the score, the greater the severity of the attack.

    We calculated the difference between the PRAM score measured one hour post treatment and the PRAM score at baseline (PRAM score 1 hour - PRAM score baseline).

    The larger the absolute value of the difference, the better the outcome (e.g., a difference of -4 indicates a better outcome that a difference of -2).

    minimum value of the difference (Albuterol - Higher Dose, experimental group): -8 maximum value of the difference (Albuterol - Higher Dose, experimental group): 0

    minimum value of the difference (Albuterol - Lower Dose, control group): -8 maximum value of the difference (Albuterol - Lower Dose, control group): 0

  3. Albuterol Determination in the Plasma

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    Albuterol determination in the plasma was carried out at at discharge or hospital admission (up to 4 hours post treatment), dosage was accomplished by High Performance Liquid Chromatography.

  4. Changes in Glucose Serum Levels

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

    Changes in glucose serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

  5. Electrocardiogram at Baseline

    Time frame: at baseline

    Electrocardiogram performed at baseline

  6. Changes in Respiratory Rate After One Hour

    Time frame: One hour post-treatment in comparison with baseline

    Change in respiratory rate one hour post-treatment in comparison with baseline.

  7. Need for Additional Therapies

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    The need for additional therapies such as magnesium sulphate or intravenous albuterol were recorded

  8. Changes in PRAM Score at Discharge or Hospital Admission

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

    Change in the Pediatric Respiratory Assessment Measure (PRAM) score at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

    The PRAM score is used to assess the severity of asthma attacks, it ranges from 0 to 15, and the higher the score, the greater the severity of the attack.

    We calculated the difference between the PRAM score measured at discharge or admission and the PRAM score at baseline (PRAM score discharge or admission - PRAM score baseline).

    The larger the absolute value of the difference, the better the outcome (e.g., a difference of -4 indicates a better outcome that a difference of -2).

    minimum value of the difference (Albuterol - Higher Dose, experimental group): -9 maximum value of the difference (Albuterol - Higher Dose, experimental group): 0

    minimum value of the difference (Albuterol - Lower Dose, control group): -9 maximum value of the difference (Albuterol - Lower Dose, control group): 1

  9. Changes in Potassium Serum Levels

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

    Changes in potassium serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

  10. Changes in Bicarbonate Serum Levels

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

    Changes in bicarbonate serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

  11. Changes in Respiratory Rate at at Discharge or Hospital Admission.

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

    Changes in respiratory rate at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

  12. Change in Pulse Oximetry One Hour Post-treatment

    Time frame: One hour post-treatment in comparison with baseline

    Change in pulse oximetry one hour post-treatment in comparison with baseline

  13. Changes in Pulse Oximetry at Discharge or Hospital Admission.

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

    Changes in pulse oximetry at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

  14. Changes in Heart Rate After One Hour

    Time frame: One hour post-treatment in comparison with baseline

    Change in heart rate one hour post-treatment in comparison with baseline.

  15. Changes in Heart Rate at Discharge or Hospital Admission

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    Changes in heart rate at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

  16. Electrocardiogram One Hour Post-treatment.

    Time frame: One hour post-treatment

    Electrocardiogram one hour post-treatment to identify possible rhythm disturbances.

  17. Electrocardiogram at Discharge or Hospital Admission

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    Electrocardiogram at discharge or hospital admission to identify possible rhythm disturbances.

  18. Lengths of Stay in the Emergency Room

    Time frame: one to four hours

    lengths of stay in the emergency room for discharged patients

  19. Admission Rates in Patients With and Without Any Virus Detected

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    Admission rates in patients with and without any of the following viruses detected by PCR in nasal lavage samples: Adenovirus; Bocavirus; Coronavirus; Enterovirus (Echovirus); Influenza (A H3N2, A H1N1/2009, B and C); Metapneumovirus (subtypes A and B); Parainfluenza 1, 2, 3 and 4 (subtypes A and B); Rhinovirus; Respiratory Syncytial Virus type A and Respiratory Syncytial Virus type B.

  20. Admission Rates in Patients With and Without Rhinovirus Detect

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    Admission rates in patients with and without rhinovirus detected by PCR in nasal lavage samples.

  21. Admission Rates in Patients With the Arg16Gly Polymorphisms

    Time frame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

    Admission rates in patients with the Arg16Gly polymorphisms of the beta-2 adrenergic receptor (Arg16Gly, Arg16Arg and Gly16Gly genotypes).

Sponsors and collaborators

Lead sponsor

University of Sao Paulo

Other

Collaborators

  • Fundação de Amparo à Pesquisa do Estado de São Paulo

Registry information

Official study title

Efficacy and Safety of Increasing Doses of Inhaled Albuterol Administered by Metered Dose Inhalers in Children With Acute Wheezing Episodes

Important dates

Study start
2011
Primary completion
2013
Study completion
2014
First posted
Mar 25, 2011
Registry last updated
Mar 14, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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