Bronchiolitis
Conditions
Keywords
Hypertonic saline, Bronchiolitis, Infants, Wheezing, Nebulized, Bronchodilator
Brief summary
The purpose of this study is to determine if nebulized hypertonic saline (or extra salty water mist) helps infants less than 12 months old hospitalized with bronchiolitis (or bad chest colds) get better enough to be discharged from the hospital sooner than those infants given nebulized normal saline (or regular salty water mist).
Detailed description
Bronchiolitis is a common admitting diagnosis for children less than 1 year of age. Although bronchiolitis has a high prevalence, there is a lack of a unified inpatient treatment plan beyond supportive care of supplemental oxygen and intravenous hydration. There have been many different approaches to the treatment of bronchiolitis, but none have conclusively proven to be beneficial. Several early studies show promise for the use of nebulized hypertonic saline, however the majority of these studies are done outside the United States and with adjunctive therapy. To date, the data suggesting that nebulized hypertonic saline is safe and effective for reducing length of stay in bronchiolitis is strong but not generalizable for the United States. The objective of this study is to conduct the first double-blind, randomized controlled trial in the United States of nebulized hypertonic saline without adjunctive therapy, including infants with bronchiolitis, including those with prior history of wheeze, to assess the effect on length of stay and therefore resource utilization.
Interventions
4 milliliters delivered via nebulizer with 5 Liters O2 flow every 4 hours until discharge
DRUG0.9% sodium chloride
4 milliliters delivered via nebulizer with 5 Liters O2 flow every 4 hours until discharge
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
Yes
Inclusion criteria
* Patients 0-12 months of age admitted to the hospital with a diagnosis of bronchiolitis.
Exclusion criteria
* status asthmaticus * chronic cardiopulmonary disease * Trisomy 21 * immunodeficiency or transplant recipient * neuromuscular disease * admission directly to the intensive care unit * previous use of nebulized hypertonic saline less than 12 hours prior to presentation * previous enrollment in the study in the 72 hours prior to presentation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay in the Study-LOS--Intention to Treat Analysis | Time of first study treatment until time of discharge | Length of stay will be defined by the duration between the time of first study treatment to the time a discharge order is placed. Alternatively, if a patient remains inpatient for other, non-bronchiolitis related reasons (i.e. social reasons, etc.) the time a patient could be discharged from the standpoint of bronchiolitis as documented by the attending, will be used. |
| Length of Stay in the Study-LOS by Per Protocol Analysis | Time of first study treatment until time of discharge | Length of stay will be defined by the duration between the time of first study treatment to the time a discharge order is placed. Alternatively, if a patient remains inpatient for other, non-bronchiolitis related reasons (i.e. social reasons, etc.) the time a patient could be discharged from the standpoint of bronchiolitis as documented by the attending, will be used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Readmission for Bronchiolitis Within 7 Days of Discharge | within 7 days of hospital discharge | Phone call at 7 days to assess for readmission to any hospital |
| Clinical Worsening | though hospitalization/time period receiving study treatment, average 2-3 days | transfer to the Pediatric Intensive Care Unit (PICU) (including withdrawn from the study for bronchodilator administration who were then transferred to the PICU), or Respiratory Distress Assessment Instrument (RDAI) increase of 4 or more points within 30 minutes of a study treatment |
| Total Adverse Events | Time of enrollment in the study through 1 week after hospital discharge | Clinical worsening events (defined prior) + 7 day readmissions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hypertonic Saline 4 mL nebulized 3% sodium chloride every 4 hours until discharge | 113 |
| Normal Saline 4 mL nebulized 0.9% sodium chloride every 4 hours until discharge | 114 |
| Total | 227 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 4 |
| Overall Study | Physician Decision | 4 | 9 |
| Overall Study | Protocol Violation | 4 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Hypertonic Saline | Normal Saline | Total |
|---|---|---|---|
| Age, Continuous | 3.86 months STANDARD_DEVIATION 3.01 | 4.39 months STANDARD_DEVIATION 2.95 | 4.1 months STANDARD_DEVIATION 2.98 |
| Sex: Female, Male Female | 36 Participants | 42 Participants | 78 Participants |
| Sex: Female, Male Male | 77 Participants | 72 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 113 | 0 / 114 |
| serious Total, serious adverse events | 13 / 113 | 10 / 114 |
Outcome results
Primary
Length of Stay in the Study-LOS by Per Protocol Analysis
Length of stay will be defined by the duration between the time of first study treatment to the time a discharge order is placed. Alternatively, if a patient remains inpatient for other, non-bronchiolitis related reasons (i.e. social reasons, etc.) the time a patient could be discharged from the standpoint of bronchiolitis as documented by the attending, will be used.
Time frame: Time of first study treatment until time of discharge
Population: Per protocol analysis (only includes participants who completed the study)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hypertonic Saline | Length of Stay in the Study-LOS by Per Protocol Analysis | 2.0 Days |
| Normal Saline | Length of Stay in the Study-LOS by Per Protocol Analysis | 2.0 Days |
p-value: 0.96Wilcoxon (Mann-Whitney)
Primary
Length of Stay in the Study-LOS--Intention to Treat Analysis
Length of stay will be defined by the duration between the time of first study treatment to the time a discharge order is placed. Alternatively, if a patient remains inpatient for other, non-bronchiolitis related reasons (i.e. social reasons, etc.) the time a patient could be discharged from the standpoint of bronchiolitis as documented by the attending, will be used.
Time frame: Time of first study treatment until time of discharge
Population: Intention to Treat Analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hypertonic Saline | Length of Stay in the Study-LOS--Intention to Treat Analysis | 2.1 Days |
| Normal Saline | Length of Stay in the Study-LOS--Intention to Treat Analysis | 2.1 Days |
p-value: 0.73Wilcoxon (Mann-Whitney)
Secondary
Clinical Worsening
transfer to the Pediatric Intensive Care Unit (PICU) (including withdrawn from the study for bronchodilator administration who were then transferred to the PICU), or Respiratory Distress Assessment Instrument (RDAI) increase of 4 or more points within 30 minutes of a study treatment
Time frame: though hospitalization/time period receiving study treatment, average 2-3 days
Population: all patients enrolled in the study were analyzed for events related to clinical worsening
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypertonic Saline | Clinical Worsening | 10 participants |
| Normal Saline | Clinical Worsening | 9 participants |
p-value: 0.97Fisher Exact
Secondary
Readmission for Bronchiolitis Within 7 Days of Discharge
Phone call at 7 days to assess for readmission to any hospital
Time frame: within 7 days of hospital discharge
Population: This population is those who completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypertonic Saline | Readmission for Bronchiolitis Within 7 Days of Discharge | 4 participants |
| Normal Saline | Readmission for Bronchiolitis Within 7 Days of Discharge | 3 participants |
p-value: 0.77Fisher Exact
Secondary
Total Adverse Events
Clinical worsening events (defined prior) + 7 day readmissions
Time frame: Time of enrollment in the study through 1 week after hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypertonic Saline | Total Adverse Events | 14 adverse events |
| Normal Saline | Total Adverse Events | 12 adverse events |
p-value: 0.67Fisher Exact
Post Hoc
LOS Analysis for Patients Whose Study Entry Respiratory Distress Assessment Instrument (RDAI) Was Greater Than or Equal to 4 or Who Had Hypoxia <92%
Time frame: through hospitalization/while receiving study medication, average 2-3 days
Population: Subgroup of patients who had a study entry Respiratory Distress Assessment Instrument (RDAI) of greater than or equal to 4 points OR hypoxia \<92% on admission
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hypertonic Saline | LOS Analysis for Patients Whose Study Entry Respiratory Distress Assessment Instrument (RDAI) Was Greater Than or Equal to 4 or Who Had Hypoxia <92% | 2.1 days |
| Normal Saline | LOS Analysis for Patients Whose Study Entry Respiratory Distress Assessment Instrument (RDAI) Was Greater Than or Equal to 4 or Who Had Hypoxia <92% | 2.1 days |
Post Hoc
LOS in Patients With a History of Previous Wheeze
Time frame: through hospitalization/while receiving study medication, average 2-3 days
Population: Subgroup of the study population who reported a history of wheezing prior to this admission
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hypertonic Saline | LOS in Patients With a History of Previous Wheeze | 1.7 days |
| Normal Saline | LOS in Patients With a History of Previous Wheeze | 2.0 days |
p-value: 0.18Wilcoxon (Mann-Whitney)
Post Hoc
LOS in Subgroup of Patients With Testing Positive for Respiratory Syncitial Virus (RSV+)
Time frame: through hospitalization/while receiving study medication, average 2-3 days
Population: This is the population in the study whose RSV testing was positive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hypertonic Saline | LOS in Subgroup of Patients With Testing Positive for Respiratory Syncitial Virus (RSV+) | 2.2 days |
| Normal Saline | LOS in Subgroup of Patients With Testing Positive for Respiratory Syncitial Virus (RSV+) | 2.0 days |
p-value: 0.39Wilcoxon (Mann-Whitney)
Post Hoc
LOS Subgroup Analysis of Patients With a History of Prematurity
Time frame: through hospitalization/while receiving study medication, average 2-3 days
Population: Patients who reported a history of prematurity/whose Gestational age was \<37 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hypertonic Saline | LOS Subgroup Analysis of Patients With a History of Prematurity | 2.9 days |
| Normal Saline | LOS Subgroup Analysis of Patients With a History of Prematurity | 2.2 days |