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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Effects on pulmonary organ function
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
Maria Clara M Barbosa
Instituto D'Or de Pesquisa
Brazil: National Committee of Ethics in Research