Clinical trial NCT01323010: Efficacy and Safety of Increasing Doses of Inhaled Albuterol in Children With Acute Wheezing Episodes
Official title: Efficacy and Safety of Increasing Doses of Inhaled Albuterol Administered by Metered Dose Inhalers in Children With Acute Wheezing Episodes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Children
Keywords: asthma
albuterol
metered dose inhalers
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2011-03-25
Enrollment: 119
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Hospital Admission
timeFrame: Starting at 4 hours post-treatment
Secondary outcomes:
measure: Forced Expiratory Volume in the First Second
timeFrame: One hour post-treatment in comparison with baseline
measure: Change in PRAM Score After One Hour
timeFrame: One hour post-treatment
measure: Albuterol Determination in the Plasma
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
measure: Changes in Glucose Serum Levels
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.
measure: Electrocardiogram at Baseline
timeFrame: at baseline
measure: Changes in Respiratory Rate After One Hour
timeFrame: One hour post-treatment in comparison with baseline
measure: Need for Additional Therapies
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
measure: Changes in PRAM Score at Discharge or Hospital Admission
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.
measure: Changes in Potassium Serum Levels
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.
measure: Changes in Bicarbonate Serum Levels
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.
measure: Changes in Respiratory Rate at at Discharge or Hospital Admission.
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.
measure: Change in Pulse Oximetry One Hour Post-treatment
timeFrame: One hour post-treatment in comparison with baseline
measure: Changes in Pulse Oximetry at Discharge or Hospital Admission.
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.
measure: Changes in Heart Rate After One Hour
timeFrame: One hour post-treatment in comparison with baseline
measure: Changes in Heart Rate at Discharge or Hospital Admission
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
measure: Electrocardiogram One Hour Post-treatment.
timeFrame: One hour post-treatment
measure: Electrocardiogram at Discharge or Hospital Admission
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
measure: Lengths of Stay in the Emergency Room
timeFrame: one to four hours
measure: Admission Rates in Patients With and Without Any Virus Detected
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
measure: Admission Rates in Patients With and Without Rhinovirus Detect
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
measure: Admission Rates in Patients With the Arg16Gly Polymorphisms
timeFrame: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto da Crianca HCFMUSP
Study officials:
affiliation: University of Sao Paulo
name: Luiz Vicente RF Silva Filho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muchao FP, Souza AV, Souza JME, Silva Filho LVRFD. Association between beta-2 adrenergic receptor variants and clinical outcomes in children and adolescents with acute asthma. Einstein (Sao Paulo). 2022 Mar 25;20:eAO6412. doi: 10.31744/einstein_journal/2022AO6412. eCollection 2022.
citation: Muchao FP, Souza JM, Torres HC, De Lalibera IB, de Souza AV, Rodrigues JC, Schvartsman C, da Silva Filho LV. Albuterol via metered-dose inhaler in children: Lower doses are effective, and higher doses are safe. Pediatr Pulmonol. 2016 Nov;51(11):1122-1130. doi: 10.1002/ppul.23469. Epub 2016 May 12.