Efficacy of Nebulised Hypertonic Saline (3%) Among Children With Bronchiolitis.

April 23, 2013 updated by: Dr. Aayush Khanal, MD

Efficacy of Nebulised Hypertonic Saline (3%) Among Children With Mild to Moderately Severe Bronchiolitis - A Double Blind Randomized Controlled Trial.

To assess the efficacy of nebulized 3% hypertonic saline in improving clinical severity scores among children aged 6 weeks to 24 months with bronchiolitis.

Study Overview

Detailed Description

Introduction and Rationale:

Bronchiolitis is a common problem with significant morbidity, and occasional mortality among young infants. Diagnostic testing, indications for hospitalization, eligibility criteria for discharge and therefore, the length of hospital stay for bronchiolitis vary globally, suggesting a lack of consensus and an opportunity to improve care for this common disorder. Likewise, despite the frequency of this condition there is no single, widely practiced, evidence-driven and universally accepted therapeutic guidelines other than supportive care. Recent studies have shown promising results regarding the role of nebulised 3% hypertonic saline in the treatment of bronchiolitis.

This therapy might obviate the need for hospital admission and reduce the length of hospital stay, if found effective. The implications of this would be that children return home early and parents return to work earlier, resulting in reduction of the morbidity and cost associated with the disease.

Trial Design This study was a prospective, interventional, parallel-assigned, double-blind, (subject,caregiver, investigator, outcome assessor) randomized controlled trial.

Ethical Clearance The study was approved by Institutional Review Board and Ethics Committee, Tribhuvan University Teaching Hospital, Institute of Medicine as well as The Institutional Review Board of Kanti Children's Hospital.

Study Participants Subjects were recruited from previously healthy children aged 6 weeks to 24 months visiting the Emergency Room and Out-Patient Department of Kanti Children Hospital with first episode of bronchiolitis.

Bronchiolitis was clinically defined as per the AAP consensus guidelines as the first episode of acute wheezing in children less than two years of age, starting as a viral upper respiratory infection (coryza, cough or fever).

Study setting The study was carried out in the Emergency Room, Observation and Out-Patient Department of Kanti Children Hospital, Kathmandu, Nepal. Recruitment occurred at the peak of bronchiolitis season in between January 15th to April 15th for duration of 4 months.

Interventions Patient enrollment occurred on weekdays (Sunday to Friday) between approximately 08.00 and 17.00 hr when, after the initial assessment, the attending pediatrician (non-study physician) called the investigator. The investigator assessed the children for eligibility, examined the children and assigned a clinical severity score described by Wang et al.

Children meeting inclusion criteria were invited to participate in the study and written informed consent was obtained from a parent or guardian.

General condition, weight, temperature, respiratory rate, heart rate, SpO2 and presence/absence of clinical dehydration were assessed in all patients and Clinical Severity score was calculated as described by Wang et al. Patients determined to be in life threatening condition were immediately managed for same and were not further considered for study.

Preparation of study drugs was done by a faculty appointed by the Department of Child Health and administration was done by an ER/OPD nurse or the investigator, and compliance with medication administration was assured by the investigator's direct observation of each nebulization.

All eligible patients were randomly assigned to one of the two groups:

  1. Group 1 (n = 50) received inhalation of L-Epinephrine 1.5 mg, diluted to 4ml with 3% Hypertonic Saline (HS) solution;
  2. Group 2 (n=50) received inhalation of L-Epinephrine, 1.5 mg, diluted to 4ml with 0.9% Normal Saline solution.

The study drug was administered at 0 and 30 min by jet nebulizers using a face mask. Prior to each drug administration and at 30, 60 and 120 min, the investigator assessed the children's general condition and recorded the CS score, SpO2 in room air, respiratory rate 60 and heart rate. All patients received the first dose of nebulization within 15- 30 minutes depending upon the time required for preparation and enrollment.

Adverse events were defined as heart rate >200, tremor, withdrawal from the study due to worsening clinical status, or discontinuation of any study medications due to side effects.

Patients were excluded from the study if the administration of the 2 courses of nebulisation was not delivered, the study drug was delayed by 10 min or more (protocol deviation) or if clinical deterioration mandated escalation of therapy and/or support.

At the end of the observation period, the attending pediatrician determined the need for hospital admission.

The parents of the patients enrolled in the study were asked to follow up after 24 hours in the OPD for repeat assessment. If the parents were not available for follow up, the investigator contacted the parents or guardians via telephone 24 hours after their ED/OPD discharge to determine the need for any unscheduled hospital visit within the next 24 hours of OPD/ ER visit: their readmission (relapse) rate.In addition, they were reassessed at the end of 1 week by telephone contact . A single investigator participated in the measurement of observations to minimize inter observer variability. All calls were made from the Hospital reception Office at appropriate times 10:00a.m. - 14:00p.m NST. Patient were labeled as Lost-to-Follow up if there was failure to communicate for 3 consecutive attempts for 2 consecutive days at their 7th and 8th day of initial presentation to the OPD/ER.

Sample Size Estimation:

Sample size was determined by the following formula :

  • n = [(z1 +z2)² (Ó1² + Ó2²) ] / (û1 - û2)²
  • Allowing a Type1 error of 5% (α :0.05), z1 score : 1.96.
  • For a Power of 95%, z2=1.64.
  • Standard deviation of the Clinical Severity Score : 1.3
  • Mean Change in Clinical Severity Score between the two interventions to consider clinically significant : Change in Clinical Severity Score of 1
  • The study proposed that a difference of 1 point in the Clinical Severity Score between the two intervention groups would be considered Clinically Significant.
  • To detect this mean difference of 1 unit in the Clinical severity score, with a Power of 95%, a Sample size of 44 in each intervention group were required.This made a total of 88 patients to be enrolled in the study.Considering the drop out/ lost to follow up to be approximately 10%, 100 patients were enrolled, allowing 50 in each group.
  • Standard deviation of the Change in clinical severity score was derived from previous studies and taken as 1.3 .

Randomization

  1. Sequence Generation A Random Allocation Software generated by computer, identified patients by a triple digit mixed numeric code was used by the study coordinator to allocate patients to treatment groups, and the study coordinator was the only person with access to the randomization.
  2. Type of Randomization Block Randomization method was used to stratify patients into blocks of 10 each, each comprising of 10 patients.

Allocation Concealment After preparation, the study solutions were labeled with the codes and wrapped in an envelope with the respective codes and attached with the proforma bearing the respective codes.Study solutions were identical in appearance and odor. The identity of the study solutions was blinded to all participants, care providers, and investigators and outcome assessor.

Implementation The randomization process was done by the study coordinator (not involved in the study) and he was the only person to have access to the codes.

The study solutions were stored in the non-freezer compartment of the refrigerator at a temperature of 2-8*C and were discarded if not used within 72 hours of preparation.

Blinding The study was a Double Blind Randomized Controlled Trial with the investigator, the participants, the nurses who delivered the drug, and the outcome assessor being blinded to the therapeutic option.

Statistical Methods The primary outcome was to detect the difference in mean change in Clinical Severity score between the two intervention groups. A power analysis revealed that, for detection of the difference of 1 unit in CS score between the 2 treatment groups, with α of 0.05 and power of 95%, we required 88 patients (44 per group).

A sample size of 100 patients was therefore chosen, with 50 patients in each group considering the possibility of loss to follow up.

Statistical analysis was performed using SPSS for Windows, Release 16.0 (SPSS Inc., Chicago, IL). Dichotomous events were analyzed by using the Chi-Square test.Dependent variables were compared by Student t-test. Statistical significance was defined as p-value < 0.05.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Bagmati Zone
      • Kathmandu, Bagmati Zone, Nepal, 44600
        • Out Patient Department and Emergency Department, Kanti Children Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 2 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 6 weeks to 24 Months.
  • First episode of wheezing
  • Fever, cough and watery nasal discharge

Exclusion Criteria :

  • Any underlying cardiovascular disease.
  • Prior wheezing.
  • Clinical Severity Score > 9.
  • Atopic dermatitis, allergic rhinitis or asthma.
  • Oxygen saturation (SpO2) <85% on room air.
  • Obtunded consciousness.
  • Previous treatment with bronchodilators within 4 hours.
  • Any steroid therapy within 48 Hours.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Standard Treatment
L-Epinephrine and Normal Saline (0.9%)
1.5ml of 1:1,000 L-Epinephrine and 4 ml of 0.9% Normal Saline
Other Names:
  • Nebulised Epinephrine in 0.9% Normal saline
Active Comparator: Study Treatment
L-Epinephrine and Hypertonic Saline (3%)
1.5ml of 1:1,000 L-Epinephrine and 4 ml of 3% Hypertonic Saline
Other Names:
  • Nebulised Epinephrine in 3% Hypertonic Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Clinical Severity Score
Time Frame: 2 hours

Mean changes in the Clinical Severity Score after 2 sessions of nebulisation as compared to baseline.

Clinical Severity Score devised by Wang et al, is an objective scoring system that measures the degree of respiratory distress in young children.

The scoring system assesses respiratory rate, wheezing, retraction, and general condition,scores ranging from 0 to 3, with higher scores indicating severe illness and vice versa.

The total scores range from 0 to 12, with increased severity receiving a higher score (Wang et al, 1992).

This scoring systems have previously been validated in a number of well designed randomized controlled trials(Anil 2010, Kuzik 2007, Sarrell 2002, and Mandelberg 2003). A 1 point improvement in the clinical severity score implies approximately 7% betterment of symptoms on the scale.

2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients Meeting Eligibility Criteria for ER/ OPD Discharge at the End of 2 Hours of Observation
Time Frame: At the end of 2 hours
At the end of 2 hours
Relapse Rate
Time Frame: 24 hours
To study the number of patients in either group who need another unscheduled medical visit within the initial 24 hours of ER/ OPD visit
24 hours
Need for Unscheduled Medical Visits, if Any, for Same Symptoms to Any Healthcare Facility Within 1 Week
Time Frame: 7 days
7 days
Missed Days of Work of Caregivers
Time Frame: 7 days
Number of patients in each intervention group whose parents reported at least 1 day of missed work due to the illness of child within the week following the initial hospital visit on 7 day follow-up call.
7 days
Persistence of Cough at the End of 1 Week
Time Frame: 7 days
Number of patients in each intervention group whose parents reported the persistence of initial cough at the end of 1 week in their children.
7 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average Duration of Crying (in Minutes) Among Babies Receiving Nebulisation Therapy.
Time Frame: 2 hours
The outcomes tries to compare the influence of duration of crying among babies receiving nebulization which interferes with drug delivery and henceforth might create a confounding bias while interpreting results.
2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Aayush Khanal, MD, Department of Child Health , Institute of Medicine , Tribhuvan University Teaching Hospital.
  • Study Director: Arun Sharma, MD, Department of Child Health , Tribhuvan University Teaching Hospital , Institute of Medicine, Maharajgunj, Kathmandu ,Nepal.
  • Study Director: Srijana Basnet, MD, Department of Child Health , Tribhuvan University Teaching Hospital , Institute of Medicine , Maharajgunj , Kathmandu , Nepal.
  • Study Chair: Pushpa R Sharma, DCH,FCPS, Head of the Department. Department of Child Health , Tribhuvan University Teaching Hospital , Institute of Medicine , Maharajgunj , Kathmandu , Nepal.
  • Study Chair: Fakir C Gami, MD, Department of Child Health, Tribhuvan University Teaching Hospital, Institute of Medicine.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

January 12, 2011

First Submitted That Met QC Criteria

January 12, 2011

First Posted (Estimate)

January 13, 2011

Study Record Updates

Last Update Posted (Estimate)

May 31, 2013

Last Update Submitted That Met QC Criteria

April 23, 2013

Last Verified

April 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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