Inhaled Steroids for the Treatment of Early Pediatric Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to show that inhaled steroids in patient with PARDS can decrease the days on mechanical ventilator measured by ventilator-free days,to improve the oxygenation index (OI) or oxygenation saturation index (OSI) in patients receiving inhaled steroids and to show the relevance and feasibility of a larger study by assessing the hypothesis in a small cohort of patients. Patient will be treated for a maximum of 10 days. Secondary objectives are to reduce the length of stay (LOS) in the pediatric intensive care unit (PICU) and hospital admissions; to show less inflammation in the patients receiving inhaled steroids by measuring inflammatory markers from tracheal aspirates like Interleukin (IL6, IL8, tumor necrosis factor (TNF) α, matrix metalloproteinase8 (MMP8) and matrix metalloproteinase9 (MMP9). Lastly, to show that inhaled steroids can improve residual lung disease evaluated by Pulmonary Function Test (PFTs) and Impulse Oscillometry (IOS).

Official Title
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Inhaled Steroids for the Treatment of Early Pediatric Acute Respiratory Distress Syndrome (PARDS), a Randomized Pilot Trial

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Budesonide
* Drug: Placebo
* Device: Nebulizer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients older than 30 days and up to 18 years of age admitted to the PICU with a diagnosis of PARDS enrolled within 72 hours of diagnosis. Patients requiring invasive mechanical ventilation. Criteria of PARDS as defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC), on June 2015 in Pediatric Critical Care Journal Exclusion Criteria: Patients with diffuse alveolar hemorrhage. Patients terminally ill with limitation of care or in hospice care. Patients receiving inhaled steroids or systemic steroids as chronic therapy before admission. Patients with high dose systemic steroids for anti-inflammatory purposes. The investigators will not exclude patients receiving hydrocortisone for shock.

Ages Eligible for Study
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Minimum Age: 30 Days
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Budesonide administered by nebulizer<br> | Drug: Budesonide<br>* Enrolled patients will be treated with Pulmicort Respules® (Budesonide inhalation suspension), at a dose of 0.5 mg, nebulized twice daily through the mechanical ventilator. The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit. The maximum length of treatment will be 10 days.<br>* Other names: Pulmicort Respules®;Device: Nebulizer<br>* The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit.<br>|
| Placebo Comparator: Placebo administered by nebulizer<br> | Drug: Placebo<br>* Enrolled patients will be treated with normal saline.The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit. The maximum length of treatment will be 10 days.<br>Device: Nebulizer<br>* The medication will be administered to the patient by the respiratory therapist with the single-patient-use medication nebulizer attached to the mechanical ventilator circuit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Ventilator-free Days (VFD) |  | Between the time of enrollment and day 28 after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation Index (OI) | Oxygenation index (OI) is calculated as ([FiO2 x Mean Airway Pressure] / PaO2). FiO2 stands for inspired fraction of oxygen, and PaO2 stands for pressure/arterial pressure of oxygen. An oxygenation index of 4-8 indicates mild ARDS, an oxygenation index of 8-16 indicates moderate ARDS, and an oxygenation index greater than 16 indicates severe ARDS. | Day one to last day of last day of mechanical ventilation (up to 10 days) | 
| Oxygen Saturation Index (OSI) | 5-7.5 mild ARDS, 7.5-12.3 moderate ARDS. > 12.3 severe ARDS, formula FiO2*Mean airway pressure/Saturation of O2 Oxygen saturation index (OI) is calculated as ([FiO2 x Mean Airway Pressure] / Saturation of oxygen). FiO2 stands for inspired fraction of oxygen. An oxygen saturation index of 5-7.5 indicates mild ARDS, an oxygen saturation index of 7.5-12.3 indicates moderate ARDS, and an oxygen saturation index greater than 12.3 indicates severe ARDS. | Day one to last day of last day of mechanical ventilation up to 28 days since enrollment | 
| Number of Days Participant Stayed in Pediatric Intensive Care Unit (PICU) |  | from time of enrollment until participant is transferred, discharged, or deceased (up to 50 days) | 
| Number of Days Participant Stayed in Hospital |  | from time of enrollment until participant is transferred, discharged, or deceased (up to 50 days) | 
| TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 1 | 
| TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 3 | 
| TNF Alpha Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | last day of treatment or last day of invasive mechanical ventilation( upto day 28) | 
| Interleukin (IL) -6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 1 | 
| IL-6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 3 | 
| IL-6 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | last day of treatment or last day of invasive mechanical ventilation( upto day 28) | 
| IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 1 | 
| IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 3 | 
| IL-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | last day of treatment or last day of invasive mechanical ventilation( upto day 28) | 
| MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 1 | 
| MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 3 | 
| MMP-8 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | last day of treatment or last day of invasive mechanical ventilation( upto day 28) | 
| MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 1 | 
| MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | Day 3 | 
| MMP-9 Levels as Assessed by the Enzyme-linked Immunosorbent Assay (ELISA) Test |  | last day of treatment or last day of invasive mechanical ventilation( upto day 28) | 
| Neutrophil Count |  | Day 1 | 
| Neutrophil Count |  | Day 3 | 
| Neutrophil Count |  | last day of treatment or last day of invasive mechanical ventilation( upto day 28) | 
| FEV1 | Forced expiration in 1st second, abnormal (obstructive)<80% L/second | 90 days since first day of treatment | 
| Forced Expiratory Volume at One Second FEV1/FVC | Restrictive disease if <70% | 90 days since first day of treatment | 
| Forced Vital Capacity (FVC) | <80% restrictive lung disease, L | 90 days since first day of treatment | 
| Forced Expiratory Flow FEF 25-75% | Medium size bronchioles, normal 60-130% | 90 days since first day of treatment | 
| Respiratory Resistance by Impulse Oscillometry (IOS) | Rrs 3-35 Hz | 90 days since first day of treatment | 
| Respiratory Impedance by Impulse Oscillometry (IOS) | Zrs 3-35 Hz | 90 days since first day of treatment | 
| Respiratory Reactance by Impulse Oscillometry (IOS) | Xrs 3-35 Hz | 90 days since first day of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Budesonide, inhaled steroids, Pediatric acute respiratory distress syndrome, PARDS