Clinical trial NCT02834819: Nebulized 3% Hypertonic Saline vs. Standard of Care in Patients With Bronchiolitis
Official title: A Randomized Controlled Trial of Nebulized 3% Hypertonic Saline vs. Standard of Care in Patients With Bronchiolitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Bronchiolitis
Keywords: bronchiolitis
hypoxia
hypertonic saline
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2016-07-15
Enrollment: 18
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether nebulized 3% hypertonic saline is more effective than the current standard of care in the treatment of viral bronchiolitis in children.

Detailed description: This will be a prospective, randomized controlled single-blinded study of patients 3-18 months of age presenting to the Children's Hospital Colorado ED during bronchiolitis season, diagnosed with mild to moderate bronchiolitis and persistent hypoxia and started on the Children's Hospital Colorado Home Oxygen pathway (see attached clinical care guideline). Investigators aim to enroll 220 patients. Patients will be identified by research assistants in the ED, based on physician diagnosis of bronchiolitis, with hypoxia requiring \< 0.5L oxygen by NC. A research assistant will approach the family and go through the informed consent process. If consent is obtained, the patient will then be randomized to one of the two study arms via a computer generated randomization table. In order to arrange for respiratory therapy, the research assistants will not be blinded. There will be an age block randomization scheme, and therefore patients aged 3-12 months will be randomized separately from patients 12.1-18 months to ensure equal distribution of age ranges in each arm.

The experimental arm will consist of patients who receive a nebulized treatment of 4ml of 3% hypertonic saline, administered by a respiratory therapist, as well as supportive care as needed. Patients in the control arm will receive supportive care only, the current standard of care at Children's Hospital Colorado. The pharmacist will randomize patients as noted above. After consent is obtained the provider will perform a pre-intervention clinical severity score evaluation to patients in both study arms utilizing the clinical severity score tool described by Wang et al.19 Respiratory therapy will then provide the nebulized treatment for those patients randomized to receive hypertonic saline. Removal of equipment following treatment will aid in ensuring blinding of physicians to treatment arm. At 90 minutes after treatment with hypertonic saline or after the order is placed for patients in the control arm, patients in both arms will undergo a second clinical severity score by the provider. At that time the provider will turn off the oxygen administered to both treatment arms for a room air challenge. The RN will be notified that the patients are off oxygen therapy and will restart oxygen if patient has saturations \< 87% (as indicated by continuous pulse oximetry) and oxygen will be restarted at 0.5L by NC.

Patients in both arms who are no longer requiring oxygen will be observed for a minimum of 4 hours to ensure they remain stable on room air, have appropriate oral intake, and sleep without de-saturation. At any point if a patient who was weaned off oxygen becomes hypoxic (saturations \< 87%), requiring \< 0.5L oxygen NC they will return to the home oxygen observation protocol. If during this period of observation any patient requires \> 0.5L oxygen during wake or sleep periods, is not taking adequate oral intake, demonstrates respiratory distress, or at physician discretion, patient may be admitted to the inpatient service for further management.

Patients in both arms will receive follow-up phone calls to assess duration and amount of oxygen, as well as adverse outcomes. Patients discharged home on room air will receive 1 phone call on post-discharge day #7 (range 6-8). Patients discharged home on oxygen will receive a phone call on day #7 (range 6-8). Calls will be made for the study by the study investigators or by the Emergency Department (ED) research assistants. During the follow-up phone call, caregivers will be asked about Primary Care Physician (PCP) follow-up visits, any future scheduled PCP visits, any adverse events including increased work of breathing, increased oxygen requirement, repeat ED visits to researchers or other institutions, outside hospital admissions, intensive care unit admission or intubations, and any instructions for weaning oxygen given by PCP. If parents have questions or concerns, these questions will be directed to a nurse, fellow, or attending provider.

Data from each subject will be collected on a data collection sheet for the follow-up phone call and PCP call. Data will then be entered into a database on a secure server and de-identified. All identifiers will be removed from the data set.

The Electronic Health Record will be reviewed to verify return visits. If return visits are documented in EPIC (electronic health records software), data on type of admission (general pediatrics or intensive care unit) and any advanced airway intervention such as intubation, continuous positive airway pressure (CPAP).

Eligibility criteria: Inclusion Criteria:

* Patients presenting to Children's Hospital Colorado ED
* ≥3 to ≤18 months of age
* Diagnosed with bronchiolitis
* Have persistent hypoxia following initial supportive care measures as outlined by Children's Hospital Colorado Bronchiolitis Clinical Care Guideline
* Started on Children's Hospital Colorado Home Oxygen Pathway

Exclusion Criteria:

* Patients who do not qualify for the Clinical Care Guideline for Home oxygen for Bronchiolitis
* Previous history of wheezing
* History of reactive airway disease
* History of underlying heart disease
* Require \>0.5L oxygen

Primary outcomes:
measure: Hospitalization Rate
timeFrame: At any point during enrollment visit or up to 7 days after enrollment visit.
measure: Number of Patients With Persistent Hypoxia
timeFrame: At baseline and 90 minutes post-intervention
measure: Need for Supplemental Oxygen After Discharge
timeFrame: At time of discharge from the hospital through 7 days.
Secondary outcomes:
measure: Pre- Intervention Clinical Severity Score
timeFrame: During Enrollment visit following randomization.
measure: Post-intervention Clinical Severity Score
timeFrame: During enrollment visit - 90 minutes after randomization
measure: Unscheduled Return ED Visits
timeFrame: Called at 7 days post enrollment visit to assess any visit within 3 days of enrollment visit
measure: Adverse Outcomes
timeFrame: During enrollment visit or within 7 days following enrollment visit
measure: Hospital Admission After Discharge
timeFrame: Within 7 days following discharge from enrollment visit
Other outcomes:
Locations:
Study officials:
affiliation: University of Colorado, Denver
name: Cortney Braund, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006 Oct;118(4):1774-93. doi: 10.1542/peds.2006-2223.
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citation: Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006458. doi: 10.1002/14651858.CD006458.pub2.
citation: Mai XM, Nilsson L, Kjellman NI, Bjorksten B. Hypertonic saline challenge tests in the diagnosis of bronchial hyperresponsiveness and asthma in children. Pediatr Allergy Immunol. 2002 Oct;13(5):361-7. doi: 10.1034/j.1399-3038.2002.01011.x.
citation: Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001506. doi: 10.1002/14651858.CD001506.pub3.
citation: Ralston S, Hill V, Martinez M. Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis. Pediatrics. 2010 Sep;126(3):e520-5. doi: 10.1542/peds.2009-3105. Epub 2010 Aug 16.