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Phase II, Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Effects and Safety of Infusion of Low-Doses of Methylprednisolone in Early ALI and ARDS in Children

Phase 2
17 Years
Not Enrolling
Acute Lung Injury, Acute Respiratory Distress Syndrome

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Trial Information

Phase II, Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Effects and Safety of Infusion of Low-Doses of Methylprednisolone in Early ALI and ARDS in Children

Scientific background. Dysregulated systemic inflammation - characterized by protracted
elevation of inflammatory cytokines in the circulation - is a key pathogenetic mechanism for
morbidity and mortality in ALI/ARDS, and is associated with tissue insensitivity and/or
resistance to inappropriately elevated endogenous glucocorticoids. In one study, prolonged
methylprednisolone treatment of ARDS patients resulted in rapid and sustained reduction in
circulating and pulmonary levels of pro-inflammatory cytokines, chemokines, and procollagen.

Preliminary work. Two recent metanalysis evaluating the use of low doses of corticosteroids
in acute lung injury/ARDS in adults reported a significant physiological improvement, a
sizable reduction in duration of mechanical ventilation and ICU length of stay and reduction
in mortality.

Hypothesis. We hypothesized that prolonged administration of low doses of methylprednisolone
in pediatric ALI/ARDS is safe and downregulates systemic inflammation and leads to earlier
resolution of pulmonary and extra pulmonary organ dysfunction and a reduction in duration of
mechanical ventilation and ICU stay.

Objective. To investigate the effects of prolonged low-dose methylprednisolone infusion on
pulmonary function (LIS and ventilation-free days), extra pulmonary organ function (PMODS
score), inflammatory markers - RCP (Reactive C Protein), IL6 (Interleukine 6), TNFα (Tumor
Necrosis Factor), IL8 (Interleukine 8), IL10 (Interleukine 10) and length of Pediatric
Intensive Care Unit (PICU) stay in early ALI/ARDS in children.

Study design. Prospective randomized, placebo-controlled, double-blind clinical trial.

Inclusion Criteria:

- Diagnosis of ALI/ARDS within the first 72 hours based on all of the following

- Respiratory failure requiring mechanical ventilation - via endotracheal
intubation or noninvasive positive pressure ventilation;

- Acute onset of bilateral pulmonary densities on chest radiograph in the context
of appropriate predisposing injury or illness with no evidence of left
ventricular failure;

- Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen
(PaO2:FiO2 ) ≤ 300 (criteria for ALI) or 200 (criteria for ARDS) with FiO2 ≥ 0,5
and PEEP = 5 cmH2O.

- To sign the Informed Consent to participate.

Exclusion Criteria:

- ALI/ARDS with more than 72 hours of diagnosis

- Failure to obtain written informed consent to participate in the study;

- Condition requiring > 0.5mg/Kg/day of prednisone equivalent (i.e., acute asthma or
bronchopulmonary dysplasia)

- Patients enrolled in another experimental (interventional) protocol within the past
30 days, which might adversely impact on the results of this study as determined by
the investigators;

- Primary or secondary neuromuscular dysfunction

- Patients using aminoglycosides combined with neuromuscular blockers

- Cardiopulmonary arrest within 7 days or anytime during present hospitalization prior
to enrollment;

- Irreversible cessation of all brain function;

- Immunosuppression, including HIV+ status, history of bone marrow or solid organ
transplantation, current malignancy, neutropenia, receiving cytotoxic therapy for any
reason, and acute burn injury;

- Severe chronic liver disease (Child-Pugh Class C score > 10 points).

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Effects on pulmonary organ function

Outcome Description:

a ≥ 1-point reduction in LIS by study day 7 or successful extubation by day 7 For patients remaining intubated on study day 7, improvement in lung function is defined as a 7-day LIS ≤ 2 (if initial LIS ≤ 2,9) or a 7-day LIS ≥ 2,5 (if initial LIS ≥ 3) Duration of mechanical ventilation defined as: ventilator free days at 28 days of entry study days of mechanical ventilation on day 28

Outcome Time Frame:

24 months

Safety Issue:


Principal Investigator

Maria Clara M Barbosa

Investigator Role:

Study Chair

Investigator Affiliation:

Instituto D'Or de Pesquisa


Brazil: National Committee of Ethics in Research

Study ID:

CONEP 16487



Start Date:

February 2013

Completion Date:

February 2016

Related Keywords:

  • Acute Lung Injury
  • Acute Respiratory Distress Syndrome
  • ALI
  • Acute Lung Injury
  • ARDS
  • Acute Respiratory Distress Syndrome
  • Pediatric Critical Care Medicine
  • Inflammatory Response
  • Respiratory Distress Syndrome, Newborn
  • Respiratory Distress Syndrome, Adult
  • Acute Lung Injury
  • Lung Injury