Bronchiolitis, ViralPhase 4NCT01247064
Hypertonic Saline for Acute Bronchiolitis
A Phase 4 study testing Nebulized 3% saline and Nebulized 0.9% Normal Saline in people with Bronchiolitis, Viral and Saline Solution, Hypertonic, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
The purpose of this study is to determine whether nebulized 3% hypertonic saline (HS) improves respiratory distress in children 2-23 months presenting to the emergency department (ED) with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol. Read more about this study
- Who is it for?
- Ages 2 to 23 months
- Conditions the study is for
- Bronchiolitis, Viral, Saline Solution, Hypertonic
- What is being tested?
- Nebulized 3% saline and Nebulized 0.9% Normal Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Dec 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 23 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 8 weeks through 23 months
- First episode of wheezing associated with respiratory distress and upper respiratory tract infection.
- Respiratory Distress Assessment Instrument (RDAI) rating of ≥4 and ≤15 after initial albuterol nebulization per standard care
- Pediatric Emergency Medicine (PEM) physician does not plan additional bronchodilator therapy within the hour after initial assessment.
- Parental/guardian permission (informed consent)
Who cannot join
- Subjects with prior history of wheezing or asthma or who have received bronchodilator therapy prior to the current illness
- Chronic lung or heart disease
- Critically ill infants requiring immediate airway stabilization
- Non-English speaking parent/guardian
- Inability to take nebulized medications
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Nebulized Hypertonic Saline for Acute Bronchiolitis in the Emergency Department
The purpose of this study is to determine whether nebulized 3% hypertonic saline (HS) improves respiratory distress in children 2-23 months presenting to the emergency department (ED) with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.
Read the detailed description
Acute bronchiolitis is the most frequent cause of infant hospitalization in the United States. Bronchiolitis typically refers to a viral lower respiratory tract infection during the first two years of life manifesting as a constellation of clinical symptoms including wheezing, cough and respiratory distress. In addition to a tremendous disease burden, bronchiolitis admissions in the United States cost more than $500 million each year.
The primary pathophysiologic processes in bronchiolitis include airway wall and peribronchial inflammation, increased mucous production, sloughing of necrotic epithelial cells, and impaired airway clearance. These processes result in airway obstruction, gas trapping, atelectasis and impaired gas exchange. Standard therapies for bronchiolitis remain supportive, including maintaining hydration and nutrition, ensuring adequate oxygenation, and physical suctioning of the nasal airways to clear secretions. Therapies such as the bronchodilator albuterol, although commonly used in standard practice, have not been proven to impact progression of disease or improve long-term outcomes of bronchiolitis.
Nebulized hypertonic saline (HS) has been shown to increase mucociliary clearance in the airways of individuals with healthy lungs. In addition nebulized HS increases airway clearance for disease processes including asthma, cystic fibrosis and bronchiectasis. A recent Cochrane review examined 4 small studies that suggest that nebulized 3% HS may reduce length of hospital stay and improve clinical severity scores in infants with acute viral bronchiolitis. None of these studies have explored the use of nebulized HS in the emergency department (ED). A recent study examined the use of a single nebulized treatment of epinephrine mixed in 3% HS in 46 infants less than 12 months presenting to the ED with bronchiolitis. This study did not find a difference between epinephrine diluted in normal saline compared to epinephrine diluted in 3% HS. Despite no effect on clinical score, the investigators did note a trend toward decreased rates of hospitalization. Furthermore, since this was the first ED study and the first negative study, the authors concluded that further investigation is necessary to determine if HS has a role in the management of acute bronchiolitis.
The purpose of the current study is to determine whether nebulized 3% HS improves respiratory distress in children 2-23 months presenting to the ED with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.
Given the tremendous clinical and financial burden of bronchiolitis, any effective therapy, particularly one that is inexpensive, has the potential to result in significant health care savings. If nebulized 3% HS improved clinical scores in the ED, this may provide an inexpensive, safe and effective therapy for children with bronchiolitis in the acute care setting.
- Conditions
- Bronchiolitis, Viral, Saline Solution, Hypertonic
- Being tested
- Nebulized 3% saline, Nebulized 0.9% Normal Saline
- Keywords
- Bronchiolitis, Hypertonic Saline
- Medical subject headings
- Bronchiolitis, Viral, Bronchiolitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nebulized 3% salineDrug
Also called 3% Hypertonic Saline Solution for Inhalation
4 mL of nebulized 3% saline once
Nebulized 0.9% Normal SalineDrug
Also called 0.9% Saline Solution for Inhalation
4 mL of 0.9% nebulized normal saline once
| Study group | Role | What they receive |
|---|---|---|
| Nebulized 3% Saline | Experimental | Not described Receives: Drug: Nebulized 3% saline |
| Nebulized 0.9% Normal Saline | Placebo comparator | Not described Receives: Drug: Nebulized 0.9% Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory Assessment Change Score (RACS)
The Respiratory Assessment Change Score (RACS) assesses change in respiratory status using the change in the Respiratory Distress Assessment Instrument (RDAI) and a standardized change in respiratory rate, with points being assigned by change increments of 10%. Thus, a change in respiratory rate of ≤5% from baseline counted as a change of 0 units, decrease/increase of 6% to 15% counted as improvement/deterioration of 1 unit, etc. The overall RACS is the arithmetic sum of the RDAI change and the standardized respiratory rate change between assessments with a decrease in RACS signifying improvement.
Measured: Baseline and 1 hour
Secondary outcomes (4)
Rate of Hospitalization
Measured: 1 day
Respiratory Rate Change
Measured: Baseline and 1 hour
Oxygen Saturation Change
Measured: Baseline and 1 hour
Parental Perception of Improvement of Breathing After Study Medication
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Bronchiolitis, ViralStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph Zorc, MD, MSCE, Principal investigator, Children's Hospital of PhiladelphiaTodd Florin, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01247064
- Sponsor's protocol ID
- IRB 10-007460
- Status last verified
- Jul 2014
- First submitted
- 15 Nov 2010
- Last updated
- 19 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Grewal S, Ali S, McConnell DW, Vandermeer B, Klassen TP. A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department. Arch Pediatr Adolesc Med. 2009 Nov;163(11):1007-12. doi: 10.1001/archpediatrics.2009.196.
PubMed 19884591Zhang 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.
PubMed 18843717Kuzik BA, Al-Qadhi SA, Kent S, Flavin MP, Hopman W, Hotte S, Gander S. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr. 2007 Sep;151(3):266-70, 270.e1. doi: 10.1016/j.jpeds.2007.04.010. Epub 2007 Jun 29.
PubMed 17719935Tal G, Cesar K, Oron A, Houri S, Ballin A, Mandelberg A. Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience. Isr Med Assoc J. 2006 Mar;8(3):169-73.
PubMed 16599051Mandelberg A, Tal G, Witzling M, Someck E, Houri S, Balin A, Priel IE. Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis. Chest. 2003 Feb;123(2):481-7. doi: 10.1378/chest.123.2.481.
PubMed 12576370Sarrell EM, Tal G, Witzling M, Someck E, Houri S, Cohen HA, Mandelberg A. Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms. Chest. 2002 Dec;122(6):2015-20. doi: 10.1378/chest.122.6.2015.
PubMed 12475841Florin TA, Shaw KN, Kittick M, Yakscoe S, Zorc JJ. Nebulized hypertonic saline for bronchiolitis in the emergency department: a randomized clinical trial. JAMA Pediatr. 2014 Jul;168(7):664-70. doi: 10.1001/jamapediatrics.2013.5306.
PubMed 24862342
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nebulized Hypertonic Saline for Acute Bronchiolitis in the Emergency Department
- ClinicalTrials.gov ID
- NCT01247064
- Acronym / sponsor ID
- IRB 10-007460
- Conditions
- Bronchiolitis, Viral, Saline Solution, Hypertonic
- Keywords
- Bronchiolitis, Hypertonic Saline
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 24 Nov 2010 (estimated)
- Results
- Posted 19 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether nebulized 3% hypertonic saline (HS) improves respiratory distress in children 2-23 months presenting to the emergency department (ED) with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.
Detailed description
Acute bronchiolitis is the most frequent cause of infant hospitalization in the United States. Bronchiolitis typically refers to a viral lower respiratory tract infection during the first two years of life manifesting as a constellation of clinical symptoms including wheezing, cough and respiratory distress. In addition to a tremendous disease burden, bronchiolitis admissions in the United States cost more than $500 million each year.
The primary pathophysiologic processes in bronchiolitis include airway wall and peribronchial inflammation, increased mucous production, sloughing of necrotic epithelial cells, and impaired airway clearance. These processes result in airway obstruction, gas trapping, atelectasis and impaired gas exchange. Standard therapies for bronchiolitis remain supportive, including maintaining hydration and nutrition, ensuring adequate oxygenation, and physical suctioning of the nasal airways to clear secretions. Therapies such as the bronchodilator albuterol, although commonly used in standard practice, have not been proven to impact progression of disease or improve long-term outcomes of bronchiolitis.
Nebulized hypertonic saline (HS) has been shown to increase mucociliary clearance in the airways of individuals with healthy lungs. In addition nebulized HS increases airway clearance for disease processes including asthma, cystic fibrosis and bronchiectasis. A recent Cochrane review examined 4 small studies that suggest that nebulized 3% HS may reduce length of hospital stay and improve clinical severity scores in infants with acute viral bronchiolitis. None of these studies have explored the use of nebulized HS in the emergency department (ED). A recent study examined the use of a single nebulized treatment of epinephrine mixed in 3% HS in 46 infants less than 12 months presenting to the ED with bronchiolitis. This study did not find a difference between epinephrine diluted in normal saline compared to epinephrine diluted in 3% HS. Despite no effect on clinical score, the investigators did note a trend toward decreased rates of hospitalization. Furthermore, since this was the first ED study and the first negative study, the authors concluded that further investigation is necessary to determine if HS has a role in the management of acute bronchiolitis.
The purpose of the current study is to determine whether nebulized 3% HS improves respiratory distress in children 2-23 months presenting to the ED with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.
Given the tremendous clinical and financial burden of bronchiolitis, any effective therapy, particularly one that is inexpensive, has the potential to result in significant health care savings. If nebulized 3% HS improved clinical scores in the ED, this may provide an inexpensive, safe and effective therapy for children with bronchiolitis in the acute care setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nebulized 3% Saline | Experimental | Drug: Nebulized 3% saline |
| Nebulized 0.9% Normal Saline | Placebo comparator | Drug: Nebulized 0.9% Normal Saline |
Who may qualify
- Ages
- 2 to 23 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Age 8 weeks through 23 months
- First episode of wheezing associated with respiratory distress and upper respiratory tract infection.
- Respiratory Distress Assessment Instrument (RDAI) rating of ≥4 and ≤15 after initial albuterol nebulization per standard care
- Pediatric Emergency Medicine (PEM) physician does not plan additional bronchodilator therapy within the hour after initial assessment.
- Parental/guardian permission (informed consent)
Key exclusion criteria (5 listed)
- Subjects with prior history of wheezing or asthma or who have received bronchodilator therapy prior to the current illness
- Chronic lung or heart disease
- Critically ill infants requiring immediate airway stabilization
- Non-English speaking parent/guardian
- Inability to take nebulized medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nebulized 3% salineAlso: 3% Hypertonic Saline Solution for Inhalation4 mL of nebulized 3% saline once | Drug | Nebulized 3% Saline |
| Nebulized 0.9% Normal SalineAlso: 0.9% Saline Solution for Inhalation4 mL of 0.9% nebulized normal saline once | Drug | Nebulized 0.9% Normal Saline |
Primary outcome
Respiratory Assessment Change Score (RACS)
Time frame: Baseline and 1 hour
The Respiratory Assessment Change Score (RACS) assesses change in respiratory status using the change in the Respiratory Distress Assessment Instrument (RDAI) and a standardized change in respiratory rate, with points being assigned by change increments of 10%. Thus, a change in respiratory rate of ≤5% from baseline counted as a change of 0 units, decrease/increase of 6% to 15% counted as improvement/deterioration of 1 unit, etc. The overall RACS is the arithmetic sum of the RDAI change and the standardized respiratory rate change between assessments with a decrease in RACS signifying improvement.
4 secondary outcomes
Rate of Hospitalization
Time frame: 1 day
Respiratory Rate Change
Time frame: Baseline and 1 hour
Oxygen Saturation Change
Time frame: Baseline and 1 hour
Parental Perception of Improvement of Breathing After Study Medication
Time frame: 1 hour
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19884591Grewal S, Ali S, McConnell DW, Vandermeer B, Klassen TP. A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department. Arch Pediatr Adolesc Med. 2009 Nov;163(11):1007-12. doi: 10.1001/archpediatrics.2009.196.
- Background: PubMed 18843717Zhang 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.
- Background: PubMed 17719935Kuzik BA, Al-Qadhi SA, Kent S, Flavin MP, Hopman W, Hotte S, Gander S. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr. 2007 Sep;151(3):266-70, 270.e1. doi: 10.1016/j.jpeds.2007.04.010. Epub 2007 Jun 29.
- Background: PubMed 16599051Tal G, Cesar K, Oron A, Houri S, Ballin A, Mandelberg A. Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience. Isr Med Assoc J. 2006 Mar;8(3):169-73.
- Background: PubMed 12576370Mandelberg A, Tal G, Witzling M, Someck E, Houri S, Balin A, Priel IE. Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis. Chest. 2003 Feb;123(2):481-7. doi: 10.1378/chest.123.2.481.
- Background: PubMed 12475841Sarrell EM, Tal G, Witzling M, Someck E, Houri S, Cohen HA, Mandelberg A. Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms. Chest. 2002 Dec;122(6):2015-20. doi: 10.1378/chest.122.6.2015.
- Derived from this study: PubMed 24862342Florin TA, Shaw KN, Kittick M, Yakscoe S, Zorc JJ. Nebulized hypertonic saline for bronchiolitis in the emergency department: a randomized clinical trial. JAMA Pediatr. 2014 Jul;168(7):664-70. doi: 10.1001/jamapediatrics.2013.5306.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Zorc, MD, MSCE principal investigator
Children's Hospital of Philadelphia
Todd Florin, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nebulized 3% saline and Nebulized 0.9% Normal Saline in people with Bronchiolitis, Viral and Saline Solution, Hypertonic, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory Assessment Change Score (RACS) (time frame: Baseline and 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01247064, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2014.