Nebulized 5% Hypertonic Saline for the Treatment of Bronchiolitis

NCT ID: NCT01016249

Last Updated: 2009-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2009-04-30

Brief Summary

The investigators reasoned that a hypertonic saline concentration higher than 3% could be safe and more efficacious in the treatment of bronchiolitis, alleviating severe symptoms and preventing the need for hospitalization in some instances.

Detailed Description

We conducted a double blind, randomized, parallel-group clinical trial to compare the efficacy and safety of hypertonic saline 3% and 5% versus normal saline for the treatment of acute bronchiolitis.

The study was conducted in the short stay unit of the Pediatric Emergency Center of Hamad General Hospital, the only pediatric emergency facility in the State of Qatar. The Center serves an average of 200,000 patients annually and manages 42 beds in the short stay unit. Patients admitted to the unit were assessed at least every 6 hours by a pediatrician to determine readiness for discharge. The length of stay in the unit for bronchiolitis range from 6 to 168 hours.

Infants aged ≤18 months presenting to the unit for the treatment of moderate-severe viral bronchiolitis were eligible for the study. Moderate-severe bronchiolitis required having a prodromal history consistent with viral upper respiratory tract infection followed by wheezing and/or crackles on auscultation and a Wang bronchiolitis severity score of ≥ 4 on presentation.

Patients were excluded from the study if they had one or more of the following characteristics: Born preterm ≤34 weeks gestation, previous history of wheezing, steroid use within 48 hours of presentation, obtundation and progressive respiratory failure requiring ICU admission, history of apnea with in 24 hours before presentation, oxygen saturation ≤ 85% on room air at the time of recruitment, history of a diagnosis of chronic lung disease, congenital heart disease, or immunodeficiency.

The six attending physicians who covered the 18 beds in the respiratory section of the short stay unit were trained in scoring and its practical application on our bronchiolitis patients in the unit before the study began.

Written and informed consent, was sought from one of the parents or legal guardians for eligible patients as soon as the patient was admitted to the unit. The study was approved by the hospital institutional review board.

Patients were examined on presentation and those requiring further treatment or observation were admitted to the short stay unit. Those with bronchiolitis were assessed for study eligibility within 2 hours of the initial physician assessment. Patients for whom consent was obtained underwent plain chest radiography and nasopharyngeal swabs were taken for RSV detection (RSV Respi-Strip, Coris Bioconcept, Gembloux, Belgium). Then a computer-generated list of random numbers was used by the enrolling physicians in consecutive order to identify a sealed envelope containing one of three codes identifying one of three different bags of 500 mL of sterilely-prepared blinded study solution, made fresh each morning by a pharmacist blinded to patient assignment.Patients received the study nebulization mixed with 1.5 ml of epinephrine in a double blinded fashion on enrollment and every 4 hours thereafter until they were ready for discharge.Additional nebulized epinephrine 5ml delivered the same way was administered with blinded study solution at a maximum frequency of every hour and additional treatment (e.g., supplementary oxygen, hydration) given at the discretion of the treating physician. Patients were withdrawn from the study if oxygen saturation within 30 min after nebulization fell below 85% on room air or clinical deterioration was determined to warrant transfer to the pediatric intensive care unit. Patients were discharged when the treating physician determined the patient did not need supplementary oxygen, was feeding adequately without intravenous fluids, and had minimal or absent wheezing, crackles, and chest retractions provided he/she had an oxygen saturation ≥ 94% and severity score < 4 on discharge.

At discharge, patients were sent home with albuterol metered-dose inhalers . Follow-up by study nurse by telephone was mandatory daily, for one week after discharge. The patient could return to the pediatric emergency center earlier if desired or needed.

Conditions

Bronchiolitis

Keywords

Bronchiolitis, Viral; An acute inflammation of the upper RESPIRATORY TRACT

Study Design

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

Study Groups

Treatment 1. 5% Saline + Epinephrine

Nebulization with 4ml of 5% saline mixed with 1.5 ml of epinephrine every 4 hours thereafter until ready for discharge. Immediately before nebulization, just after, and 2 hours after, the following measurements were collected for each patients: bronchiolitis severity score, oxygen saturation on room air, and heart rate.

Group Type: ACTIVE_COMPARATOR

Treatment 1. (5% Hypertonic saline + Epinephrine)

Intervention Type: DRUG

Nebulization of 4ml 5% saline mixed with 1.5 ml of epinephrine on enrollment and every 4 hours thereafter until ready for discharge.

Treatment 3. 3% Saline + Epinephrine

Nebulization with 4ml of 3% saline mixed with 1.5 ml of epinephrine every 4 hours thereafter until ready for discharge. Immediately before nebulization, just after, and 2 hours after, the following measurements were collected for each patients: bronchiolitis severity score, oxygen saturation on room air, and heart rate.

Group Type: OTHER

Treatment 3. (3% Hypertonic saline + Epinephrine)

Intervention Type: DRUG

Nebulization of 4ml 3% saline mixed with 1.5 ml of epinephrine on enrollment and every 4 hours thereafter until ready for discharge.

Treatment 2 . 0.9% Saline + Epinephrine

Nebulization with 4ml of 0.9% saline mixed with 1.5 ml of epinephrine every 4 hours thereafter until ready for discharge. Immediately before nebulization, just after, and 2 hours after, the following measurements were collected for each patients: bronchiolitis severity score, oxygen saturation on room air, and heart rate.

Group Type: OTHER

Treatment 2. (Normal saline + Epinephrine)

Intervention Type: DRUG

Nebulization of 4ml 0.9% saline mixed with 1.5 ml of epinephrine on enrollment and every 4 hours thereafter until ready for discharge.

Interventions

Treatment 1. (5% Hypertonic saline + Epinephrine)

Nebulization of 4ml 5% saline mixed with 1.5 ml of epinephrine on enrollment and every 4 hours thereafter until ready for discharge.

Intervention Type: DRUG

Treatment 3. (3% Hypertonic saline + Epinephrine)

Nebulization of 4ml 3% saline mixed with 1.5 ml of epinephrine on enrollment and every 4 hours thereafter until ready for discharge.

Intervention Type: DRUG

Treatment 2. (Normal saline + Epinephrine)

Nebulization of 4ml 0.9% saline mixed with 1.5 ml of epinephrine on enrollment and every 4 hours thereafter until ready for discharge.

Intervention Type: DRUG

Other Intervention Names

5% Hypertonic saline; 3% Hypertonic saline; Normal saline

Eligibility Criteria

Inclusion Criteria

• Infants aged ≤ 18 months presenting to the unit for the treatment of moderate-severe viral bronchiolitis were eligible for the study.
• Moderate-severe bronchiolitis required having a prodromal history consistent with viral upper respiratory tract infection followed by wheezing and/or crackles on auscultation and a Wang bronchiolitis severity score of ≥ 4 on presentation.

Exclusion Criteria

Patients were excluded from the study if they had one or more of the following characteristics:

• Born preterm ≤ 34 weeks gestation,
• Previous history of wheezing,
• Steroid use within 48 hours of presentation,
• Obtundation and progressive respiratory failure requiring ICU admission,
• History of apnea with in 24 hours before presentation,
• Oxygen saturation ≤ 85% on room air at the time of recruitment,
• History of a diagnosis of chronic lung disease,
• Congenital heart disease, or
• Immunodeficiency.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamad Medical Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Hamad Medical Corporation

Principal Investigators

Khalid M. Al-Ansari, FRCPC,FAAP

Role: PRINCIPAL_INVESTIGATOR

Hamad Medical Corporation, Weill Cornell Medical College

Locations

Pediatric Emergency Center, Al-Saad

Doha, Baladīyat ad Dawḩah, Qatar

Countries

Qatar

References

Al-Ansari K, Sakran M, Davidson BL, El Sayyed R, Mahjoub H, Ibrahim K. Nebulized 5% or 3% hypertonic or 0.9% saline for treating acute bronchiolitis in infants. J Pediatr. 2010 Oct;157(4):630-4, 634.e1. doi: 10.1016/j.jpeds.2010.04.074. Epub 2010 Jun 19.

Reference Type: DERIVED

PMID: 20646715 (View on PubMed)

Other Identifiers

#7055

Identifier Type: -

Identifier Source: org_study_id