Trial of Steroids in Pediatric Acute Lung Injury/ARDS

Phase 2

• Conditions: Acute Respiratory Distress Syndrome (ARDS); Acute Lung Injury (ALI)
• Interventions: Drug: Normal Saline (0.9%); Drug: methylprednisolone

• Registration Number: NCT01274260
• Lead Sponsor: University of Tennessee

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-01-09
• Study First Submitted QC: 2011-01-10
• Study First Posted: 2011-01-11
• Primary Completion: 2014-01
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-23
• Last Update Posted: 2014-05-28
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Between 1 month and 18 years of age; AND

2. Admitted to the PICU with a diagnosis of ALI or ARDS, as defined by:

   1. acute onset of the disease,
   2. PaO2/FiO2 ratio <300,
   3. evidence of bilateral infiltrates on chest radiography, and
   4. no evidence of cardiac dysfunction; AND

3. Intubated and mechanically ventilated.

Exclusion Criteria

1. Underlying disease requiring steroids >0.5mg/kg/day of methylprednisolone (eg. Asthma)
2. HIV positive, or have any other congenital or acquired immunodeficiency;
3. Terminally ill patients or patients on hospice care or if there is a lack of commitment to aggressive intensive care
4. Cytotoxic therapy within the past 3 weeks
5. Major gastrointestinal bleeding within last 1 month
6. Extensive burns (>20% total body surface area of full- or partial-thickness burns)
7. Known or suspected adrenal insufficiency
8. Vasculitis or diffuse alveolar hemorrhage
9. Bone marrow or lung transplant
10. Disseminated fungal infections
11. Severe chronic liver disease
12. Other conditions with estimated 6-month mortality of 50% or higher

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	Normal Saline (0.9%)	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.
Experimental Group	methylprednisolone	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.

Primary Outcome Measures

Name	Time	Method
Duration of mechanical ventilation	0-28 days	Number of hours required for positive pressure ventilation after the start of study drug

Secondary Outcome Measures

Name	Time	Method
Incidence of nosocomial infections	0-35 days	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.
Improvement in oxygenation	0-28 days	Differences in the PaO2/FiO2 ratios between the two randomized groups
Incidence of hyperglycemia	0-28 days	Number of times that the subject has a Blood Glucose \>180 mg/dL (10 mmol/L) will be compared between the randomized groups

Trial Locations

Locations (1)

Le Bonheur Children's Hospital; 🇺🇸 Memphis, Tennessee, United States