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

NCT ID: NCT01323010

Last Updated: 2016-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-04-30

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.

Conditions

Asthma; Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Albuterol - Experimental

Albuterol dosages during the first hour include 900 mcg (up to 15 kg), 1200 mcg (\> 15 to 20 kg), 1500 mcg (\> 20 to 25 kg) and 1800 mcg (\> 25 kg).

Group Type: EXPERIMENTAL

Albuterol - Experimental

Intervention Type: 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).

Albuterol - Control

Albuterol dosages during the first hour include either 600 mcg (up to 25 kg) or 1200 mcg (\> 25 kg).

Group Type: ACTIVE_COMPARATOR

Albuterol - Control

Intervention Type: 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)

Interventions

Albuterol - Experimental

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).

Intervention Type: DRUG

Albuterol - Control

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)

Intervention Type: DRUG

Other Intervention Names

Ventolin; Ventolin

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Luiz Vicente Ribeiro Ferreira da Silva Filho

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luiz Vicente RF Silva Filho, MD

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo

Locations

Instituto da Crianca HCFMUSP

São Paulo, São Paulo, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 35352766 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27171324 (View on PubMed)

Other Identifiers

Hidalba

Identifier Type: -

Identifier Source: org_study_id