Epinephrine, Dexamethasone, and Hypertonic Saline in Bronchiolitis, Randomised Clinical Trial of Efficacy and Safety

NCT ID: NCT01834820

Last Updated: 2015-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-06-30

Brief Summary

In infancy, bronchiolitis is the most common acute infection of the lower respiratory Tract. The current treatment of bronchiolitis is controversial. Bronchodilators and corticosteroids are widely used but not routinely recommended. Hypertonic saline is currently the only drug recommended by the Spanish Association of Pediatrics in treatment guidelines.

The purpose of this study is quantify whether epinephrine, dexamethasone, and hypertonic saline are effective to decrease the rate of hospital admissions at seven day, also verify adverse effects in patients submitted.

Detailed Description

Infections remain the leading cause of death globally, in 2010 from 7.6 million deaths in children under 5 years, 64% is attributed to an infectious cause, acute lower respiratory tract include 14.1% of all deaths, representing the leading cause of global mortality in children. In Mexico in children under 15 years the leading cause of death are conditions originating in the perinatal period, congenital malformations deformities and chromosomal abnormalities and third lower airway infections.

Bronchiolitis being the leading cause of lower respiratory tract infection in infants, with a global load elevated, represented by a hospitalization rate of 3% of the total population of children under one year. Estimated that only in the United States of America, the annual cost of hospitalizations of patients under one year with bronchiolitis exceeds $ 700 million / year. Unfortunately, there is evidence that hospital admission rates have increased almost twice in the last 10-15 years in the United States and Canada, and it occurs most impact in developing countries, where befall 99% of deaths related to Respiratory Syncytial Virus (RSV), the leading cause of infection of lower airways.

The etiology of the disease is attributed by 50 to 80% of all cases the RSV worldwide, has been reported in Mexico RSV as a cause of just over 80% of infections lower airway requiring hospitalization.

Given such alarming morbidity figures, note that the mortality from this disease is low, representing less than 400 deaths annually, perhaps explained by the wide clinical spectrum that presents.

Currently no management guide recommends specific treatment for bronchiolitis, in particular, it is necessary to mention the national clinical practice guideline, which emphasizes that there is no consensus on proper drug treatment for this disease.

Until 2006, the American Academic of Pediatrics guidelines and Scottish Intercollegiate Guidelines Network recommend not using any systemic or inhaled drug for the management of bronchiolitis, this widely shown including bronchodilators, corticosteroids, antivirals and antitussive.

Recent review of Cochrane Acute Respiratory Infections Group about benefit of glucocorticoids for acute viral bronchiolitis, concluded not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo and there was no benefit in length of stay for inpatients; however unadjusted results from a large factorial low risk o bias Randomized Controlled Trial found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions 26% with no differences in short-term adverse effects.

L. Hartling et al, in 2011 review demonstrates the superiority of epinephrine compared to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care.

In Mexico there is evidence of the use of dexamethasone in combination with inhaled salbutamol in the management of patients with bronchiolitis with decreased hospital stay to 24hrs 96% vs 75% at P <0.05

Furthermore, hypertonic saline (HS) has proven effective with minimal adverse effects and thus, currently the clinical practice guidelines of Spain in 2010, are the only recommended method.

A study conducted by Ipek et al, a comparative study with four treatment groups I Salbutamol + Normal Saline 0.9% (NS), Group II Salbutamol + HS, Group III HS and Group IV NS, with the measurement variables heart rate, respiratory difficulty scale, and oxygen saturation, found that after treatment in all groups were significant improvement in breathlessness p <0.0001. These findings demonstrate the self-limiting nature of disease, bringing the ethical basis using NS as a control group because, per se, significantly reduces respiratory distress and as indicated by the clinical practice guidelines as part of management symptomatic.

Therefore this research aims to be a pilot study to the population of Marina, first, get the best treatment evidence, using treatments that have reported better results in order to establish optimal treatment to reduce the rate of hospital admissions and with minimal adverse effects.

Included in the study, patients with mild to moderate bronchiolitis, defining it as the first event of wheezing in infants under two years with a history of viral infection prodrome attending the emergency department (ED) the period January to April in 2013.

Supportive care including oxygen supplementation if oxygen saturation less than 92% while breathing ambient; aspiration, temperature control and hydration when necessary were provided to all patients. Infants 2 to 24 months of age with bronchiolitis who were seen at emergency department were eligible for the study if they had a score of 2 to 8 on the Clinical Bronchiolitis Severity Scores (CBSS). The CBSS values the respiratory distress with respiratory rate, wheezing, general condition and presence of retractions on a scale from 0 to 12, with higher scores indicating more severe illness; an a score above 9 very severe illness.

All eligible patients were randomly assigned to one of three groups according to the consecutive order of their admission to the ED: group I received first day one treatment of nebulized dexamethasone and two treatments of epinephrine, followed by three days one treatment nebulized dexamethasone; Group II the first day received three nebulized HS followed by treatment with HS every 24 hours for 3 days and group 3 received only NS first day 3 treatments followed one treatment every 24hrs for 3 days. The nebulized solution was administered in a double-blind setting every 20 min until 3 doses had been administered (0, 20 and 40th min).

The research recorded the patient's CBSS score, respiratory rate, heart rate, and oxygen saturation in ambient air at baseline, between the three nebulizations, and at 60 and 90 minutes; rectal temperature at baseline and 90 minutes; blood pressure at baseline and 90 minutes; and any side effects throughout the observation period in the emergency department.

Followed up each patient to record the admission rate in each group at 7 days of the study, as measure of efficacy of treatment. Likewise measured the potential adverse effects of each group, including hypertension, bronchospasm, tachycardia and any eventuality, as a security measure

Conditions

Bronchiolitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: TRIPLE

Study Groups

Epinephrine and Dexamethasone

First day: One treatment of nebulized dexamethasone 4mg (1ml of dexamethasone 8mg/2ml) + 3ml NS, followed by two treatments of nebulized epinephrine (3 ml of epinephrine in a 1:1000 solution per treatment) with interval 20 minutes. And one treatment of nebulized dexamethasone every 24h for three days.

Group Type: EXPERIMENTAL

Epinephrine and Dexamethasone

Intervention Type: DRUG

Hypertonic Saline 3%

3 treatments of nebulized HS 3% 4ml in first day of treatment with interval 20 minutes And one treatment of nebulized HS 3% 4ml every 24 hours for 3 days

Group Type: EXPERIMENTAL

Hypertonic Saline

Intervention Type: DRUG

Normal Saline 0.9%

3 treatments of nebulized Normal Saline 0.9% 4ml in first day of treatment with interval 20 minutes. And one treatment of nebulized Normal Saline 0.9% 4ml every 24 hours for 3 days

Group Type: ACTIVE_COMPARATOR

Normal Saline

Intervention Type: DRUG

Interventions

Epinephrine and Dexamethasone

Intervention Type: DRUG

Hypertonic Saline

Intervention Type: DRUG

Normal Saline

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients under 2 years of age diagnosed with bronchiolitis
• Be beneficiaries Marine
• Outpatient
• Severity of Bronchiolitis mild to moderate scale according to Wood-Downes

Exclusion Criteria

• Patients with a history of atopy
• Patients with a history of asthma in infants
• Patients with serious bacterial illness criteria
• Patients with comorbidity

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital General Naval de Alta Especialidad - Escuela Medico Naval

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

José Luis Rodríguez Cuevas, pediatrician

Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital General Naval de Alta Especialidad

Mexico City, Mexico City, Mexico

Countries

Mexico

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Other Identifiers

HGNAE-01

Identifier Type: -

Identifier Source: org_study_id