Back to resultsTrial of Steroids in Pediatric Acute Lung Injury/ARDS (SPALIT)
Primary Purpose
Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury (ALI)
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
methylprednisolone
Normal Saline (0.9%)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome (ARDS) focused on measuring child, infant, lung injury, inflammation, pneumonia, ventilator
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
Sites / Locations
- Le Bonheur Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Experimental Group
Placebo Group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Duration of mechanical ventilation
Number of hours required for positive pressure ventilation after the start of study drug
Secondary Outcome Measures
Improvement in oxygenation
Differences in the PaO2/FiO2 ratios between the two randomized groups
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01274260
Brief Title
Trial of Steroids in Pediatric Acute Lung Injury/ARDS
Acronym
SPALIT
Official Title
Steroids in Pediatric Acute Lung Injury/ARDS Trial: A Blinded, Placebo-controlled, Randomized Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Unknown status
Study Start Date
October 2010 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
December 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Tennessee
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury (ALI)
Keywords
child, infant, lung injury, inflammation, pneumonia, ventilator
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental Group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Normal Saline (0.9%)
Intervention Description
The placebo will be 0.9% (normal) saline and the active medication will be diluted in 0.9% (normal) saline.
Primary Outcome Measure Information:
Title
Duration of mechanical ventilation
Description
Number of hours required for positive pressure ventilation after the start of study drug
Time Frame
0-28 days
Secondary Outcome Measure Information:
Title
Improvement in oxygenation
Description
Differences in the PaO2/FiO2 ratios between the two randomized groups
Time Frame
0-28 days
Title
Incidence of nosocomial infections
Description
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.
Time Frame
0-35 days
Title
Incidence of hyperglycemia
Description
Number of times that the subject has a Blood Glucose >180 mg/dL (10 mmol/L) will be compared between the randomized groups
Time Frame
0-28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Le Bonheur Children's Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27066464
Citation
Kimura D, Saravia J, Rovnaghi CR, Meduri GU, Schwingshackl A, Cormier SA, Anand KJ. Plasma Biomarker Analysis in Pediatric ARDS: Generating Future Framework from a Pilot Randomized Control Trial of Methylprednisolone: A Framework for Identifying Plasma Biomarkers Related to Clinical Outcomes in Pediatric ARDS. Front Pediatr. 2016 Mar 31;4:31. doi: 10.3389/fped.2016.00031. eCollection 2016.
Results Reference
derived
PubMed Identifier
26545141
Citation
Schwingshackl A, Kimura D, Rovnaghi CR, Saravia JS, Cormier SA, Teng B, West AN, Meduri UG, Anand KJ. Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial. Cytokine. 2016 Jan;77:63-71. doi: 10.1016/j.cyto.2015.10.007. Epub 2015 Nov 3.
Results Reference
derived
PubMed Identifier
25634565
Citation
Drago BB, Kimura D, Rovnaghi CR, Schwingshackl A, Rayburn M, Meduri GU, Anand KJ. Double-blind, placebo-controlled pilot randomized trial of methylprednisolone infusion in pediatric acute respiratory distress syndrome. Pediatr Crit Care Med. 2015 Mar;16(3):e74-81. doi: 10.1097/PCC.0000000000000349.
Results Reference
derived
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Trial of Steroids in Pediatric Acute Lung Injury/ARDS
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