Trial of Steroids in Pediatric Acute Lung Injury/ARDS

Study Overview
=================
Brief Summary
-----------------
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating disorders associated with lung inflammation, low oxygen levels and respiratory failure in children. Prevalence of ALI ranges from 2.2 to 12 per 100,000 children per year. Using these estimates, up to 9,000 children each year will develop ALI/ARDS, which may cause upto 2,000 deaths per year. Currently, there are no specific therapies directed against ARDS/ALI in children. In adult patients, use of steroids early in the course of ARDS appears promising. There are no published clinical trials examining the use of steroids for the treatment of ALI/ARDS in children. Hypothesis: Subjects with ALI/ARDS receiving steroids early in the course of disease (within 72 hours) and longer than 7 days will have improved clinical outcomes as compared to placebo control group as defined by (a) a decreased duration of mechanical ventilation and (b) significantly increased PaO2/FiO2 ratios.

Official Title
-----------------
Steroids in Pediatric Acute Lung Injury/ARDS Trial: A Blinded, Placebo-controlled, Randomized Clinical Trial

Conditions
-----------------
Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury (ALI)

Intervention / Treatment
-----------------
* Drug: methylprednisolone
* Drug: Normal Saline (0.9%)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Between 1 month and 18 years of age; AND Admitted to the PICU with a diagnosis of ALI or ARDS, as defined by: acute onset of the disease, PaO2/FiO2 ratio <300, evidence of bilateral infiltrates on chest radiography, and no evidence of cardiac dysfunction; AND Intubated and mechanically ventilated. Exclusion Criteria: Underlying disease requiring steroids >0.5mg/kg/day of methylprednisolone (eg. Asthma) HIV positive, or have any other congenital or acquired immunodeficiency; Terminally ill patients or patients on hospice care or if there is a lack of commitment to aggressive intensive care Cytotoxic therapy within the past 3 weeks Major gastrointestinal bleeding within last 1 month Extensive burns (>20% total body surface area of full- or partial-thickness burns) Known or suspected adrenal insufficiency Vasculitis or diffuse alveolar hemorrhage Bone marrow or lung transplant Disseminated fungal infections Severe chronic liver disease Other conditions with estimated 6-month mortality of 50% or higher

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental Group<br>Intervention: Subjects in this study group will receive a loading dose of methylprednisolone 2mg/kg followed by 1mg/kg/day of methylprednisolone infusion from day 1 to day 7; 0.5mg/kg/d from days 8 to 10, 0.25mg/kg/d on days 11 and 12, 0.125mg/kg/d on days 13 and 14. The study drug infusion will be discontinued after 14 days. | Drug: methylprednisolone<br>* Subjects in this group will receive a loading dose of methylprednisolone 2mg/kg followed by 1mg/kg/day of methylprednisolone infusion from day 1 to day 7; 0.5mg/kg/d from days 8 to 10, 0.25mg/kg/d on days 11 and 12, 0.125mg/kg/d on days 13 and 14. The study drug infusion will be discontinued after 14 days.<br>|
| Placebo Comparator: Placebo Group<br>Intervention: The placebo will be 0.9% (normal) saline and the active medication will be diluted in 0.9% (normal) saline. The placebo group with receive the masked study drug in infusion rates that mimic the infusions received by the experimental group. | Drug: Normal Saline (0.9%)<br>* The placebo will be 0.9% (normal) saline and the active medication will be diluted in 0.9% (normal) saline.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of mechanical ventilation | Number of hours required for positive pressure ventilation after the start of study drug | 0-28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in oxygenation | Differences in the PaO2/FiO2 ratios between the two randomized groups | 0-28 days | 
| Incidence of nosocomial infections | Infection surveillance will be in the form of tracheal aspirate for gram stain and culture done prior to study entry and then every 3-5 days. If a subject spikes a fever during the study drug infusion, they will have blood, urine and tracheal aspirate cultures done along with CBC and CRP. Number of nosocomial infections documented via surveillance cultures will be compared between groups. | 0-35 days | 
| Incidence of hyperglycemia | Number of times that the subject has a Blood Glucose >180 mg/dL (10 mmol/L) will be compared between the randomized groups | 0-28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
child, infant, lung injury, inflammation, pneumonia, ventilator