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Technical difficulties (reduced staff plus university strike)
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Acute viral bronchiolitis is an extremely common childhood disease, responsible for approximately 17% of childhood admissions to hospital per year, with an annually cost that reaches U$ 500 million.
Despite being a well known disease among pediatricians, there are few, if any, effective treatment options apart from oxygen supplementation and adequate hydration.
The purpose of this study is to determine wether nebulized hypertonic saline (3%) is more effective than normal saline (0,9%) when used in repeated doses during the first 24 hours of in-hospital treatment.
Acute viral bronchiolitis is a lower airway infection, caused manly by Respiratory Syncytial Virus. Near 1% of children up to 2 years of age get it with sufficient severity to warrant hospital admission, with an annual cost of about U$ 500 million in the US, superior, for instance, than cystic fibrosis annual cost.
Despite the physiopathology and clinical course being well known among pediatricians, few therapeutical options other than adequate hydration and oxygen supplementation have proven to be effective Corticosteroids are not effective and bronchodilators are controversial, and treatment is still mostly empiric and lacking evidence.
In the last few years, there has been a growing interest in the use of nebulized hypertonic saline (HS) as a promising approach. The rational is that HS would help reducing edema and mucus viscosity, enhancing its rheologic properties. Recent studies suggest that HS could reduce up to 1 day (25%) of time until discharge in admitted patients. In the Emergency Department, HS was not superior to other forms of treatment, but these studies lack power and similarities to draw further conclusions. Also, time of treatment and ideal interval between doses are not known as yet.
To our knowledge, few if any studies have assessed patients with an intermediary (up to 24h) time of stay, namely a short stay ward attached to an emergency department. Thus, we have endeavoured to determine if repeated doses of nebulized HS are superior to nebulized normal saline (NS) during the first 24 hour of treatment, when considered: rate of admission, time until discharge, time until attain discharge criteria, and rate of readmission after discharge.
Furthermore, most studies use HS associated to a bronchodilator, because of a theoretical possibility that HS alone could induce bronchoconstriction and worsen respiratory symptoms. However, recent studies have shown that HS use without bronchodilators have not caused any worsening of symptoms in bronchiolitis patients. Therefore, we propose to study the effect of HS alone, without the adding of bronchodilators, which would minimize bias in the treatment group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal Saline | Placebo Comparator | Patients will receive inhaled normal saline, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. |
|
| Hypertonic Saline | Experimental | Patients will receive inhaled Hypertonic Saline 3%, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hypertonic Saline | Drug | Sodium Chloride 3% solution, previously prepared in 5 mL syringes. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Admission | Patients staying longer than 24h are considered to be admitted to ward. | 24 hours |
| Time to Attain Discharge Criteria | Discharge criteria are: Room air saturation >94% AND respiratory rate < 60 AND Respiratory Distress Assessment Instrument (RDAI) score inferior than 4, maintained over a 4 hour period. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Discharge | Actual time to discharge was considered of secondary importance as it can be influenced by individual considerations like patient age or time of the day. | 24 hours |
| Rate of Readmission After Discharge |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mateus D Leme, MD | Sao Paulo University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Sao Paulo University | São Paulo | São Paulo | 05508-000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19953579 | Background | Anil AB, Anil M, Saglam AB, Cetin N, Bal A, Aksu N. High volume normal saline alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal saline, and 3% saline in mild bronchiolitis. Pediatr Pulmonol. 2010 Jan;45(1):41-7. doi: 10.1002/ppul.21108. | |
| 12576370 | Background | Mandelberg 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. |
| Label | URL |
|---|---|
| University Hospital of Sao Paulo University | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Saline | Patients will receive inhaled normal saline, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate |
| FG001 | Hypertonic Saline | Patients will receive inhaled Hypertonic Saline 3%, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Hypertonic Saline: Sodium Chloride 3% solution, previously prepared in 5 mL syringes. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Number of patients completing the study was too low to make statistically significant comparisons.
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Saline | Patients will receive inhaled normal saline, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Rate of Admission | Patients staying longer than 24h are considered to be admitted to ward. | Number of participants analyzed was too small to obtain statistic significance | Posted | Number | participants | 24 hours |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normal Saline | Patients will receive inhaled normal saline, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mateus Deckers Leme | Hospital Universitario - Sao Paulo University | X551130919200 | 9451 | mateusdl@gmail.com |
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| ID | Term |
|---|---|
| D001988 | Bronchiolitis |
| ID | Term |
|---|---|
| D001991 | Bronchitis |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
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| ID | Term |
|---|---|
| D012462 | Saline Solution, Hypertonic |
| D014965 | X-Rays |
| ID | Term |
|---|---|
| D006982 | Hypertonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D060733 | Electromagnetic Radiation |
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| Chest X-Ray | Radiation |
|
| Respiratory virus screening test | Other | Immunofluorescence analysis of nasal aspirate |
|
The mere attendance to the Emergency Department will not be isolately considered, as it may be due to a scheduled reevaluation.
| 5 days |
| Incidence of Adverse Effects | Any adverse effects directly attributable to treatment shall be noted. Mere lack of improve or worsening of symptoms attributable to the disease clinical course will not be considered as adverse effects. | 24 hours |
| 17719935 | Background | Kuzik 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. |
| 23900970 | Background | Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2013 Jul 31;(7):CD006458. doi: 10.1002/14651858.CD006458.pub3. |
| 21633141 | Background | Principi T, Komar L. A critical review of "a randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department.". J Popul Ther Clin Pharmacol. 2011;18(2):e273-4. Epub 2011 May 16. No abstract available. |
| 24344111 | Background | Jacobs JD, Foster M, Wan J, Pershad J. 7% Hypertonic saline in acute bronchiolitis: a randomized controlled trial. Pediatrics. 2014 Jan;133(1):e8-13. doi: 10.1542/peds.2013-1646. Epub 2013 Dec 16. |
| 20014350 | Background | Mandelberg A, Amirav I. Hypertonic saline or high volume normal saline for viral bronchiolitis: mechanisms and rationale. Pediatr Pulmonol. 2010 Jan;45(1):36-40. doi: 10.1002/ppul.21185. No abstract available. |
| 21073773 | Background | Kuzik BA, Flavin MP, Kent S, Zielinski D, Kwan CW, Adeleye A, Vegsund BC, Rossi C. Effect of inhaled hypertonic saline on hospital admission rate in children with viral bronchiolitis: a randomized trial. CJEM. 2010 Nov;12(6):477-84. doi: 10.1017/s1481803500012690. |
| BG001 | Hypertonic Saline | Patients will receive inhaled Hypertonic Saline 3%, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Hypertonic Saline: Sodium Chloride 3% solution, previously prepared in 5 mL syringes. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Hypertonic Saline |
Patients will receive inhaled Hypertonic Saline 3%, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Hypertonic Saline: Sodium Chloride 3% solution, previously prepared in 5 mL syringes. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate |
|
|
| Primary | Time to Attain Discharge Criteria | Discharge criteria are: Room air saturation >94% AND respiratory rate < 60 AND Respiratory Distress Assessment Instrument (RDAI) score inferior than 4, maintained over a 4 hour period. | Not Posted | 24 hours |
| Secondary | Time to Discharge | Actual time to discharge was considered of secondary importance as it can be influenced by individual considerations like patient age or time of the day. | Not Posted | 24 hours |
| Secondary | Rate of Readmission After Discharge | The mere attendance to the Emergency Department will not be isolately considered, as it may be due to a scheduled reevaluation. | Not Posted | 5 days |
| Secondary | Incidence of Adverse Effects | Any adverse effects directly attributable to treatment shall be noted. Mere lack of improve or worsening of symptoms attributable to the disease clinical course will not be considered as adverse effects. | Number of patients too small to achieve statistical significance | Posted | Number | participants | 24 hours |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Hypertonic Saline | Patients will receive inhaled Hypertonic Saline 3%, initially with a 2 hour interval, and clinical evaluation prior to each inhalation. When they attain sat>94% AND respiratory rate <60 AND RDAI score <4, the interval between inhalations will be changed to 4 hours. If they maintain these criteria for a whole 4 hour interval, they are discharged. If they do not improve enough to be discharged in 24 hours from the first inhalation, they are considered as admitted to hospital. Hypertonic Saline: Sodium Chloride 3% solution, previously prepared in 5 mL syringes. Chest X-Ray Respiratory virus screening test: Immunofluorescence analysis of nasal aspirate | 0 | 14 | 0 | 14 |
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| D012140 |
| Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D055590 |
| Electromagnetic Phenomena |
| D060328 | Magnetic Phenomena |
| D055585 | Physical Phenomena |
| D011827 | Radiation |
| D011839 | Radiation, Ionizing |