Scientific background. Dysregulated systemic inflammation 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. Five randomized trials (N = 518) investigating prolonged glucocorticoid
treatment in acute lung injury/ARDS reported a significant physiological improvement and a
sizable reduction in duration of mechanical ventilation and ICU length of stay. Insufficient
data is available on the effects of low dose prolonged methylprednisolone treatment initiated
in early ALI/ARDS on mortality.
Hypothesis. We hypothesized that the anti-inflammatory activity associated with prolonged
methylprednisolone administration improves pulmonary and extra-pulmonary organ dysfunction in
early ALI/ARDS and reduces mortality.
Objective. To investigate the effects of prolonged low-dose methylprednisolone infusion on
mortality and morbidity in early ALI/ARDS.
Study design. Multicenter, prospective randomized, placebo-controlled, double-blind clinical
trial.
Entry criteria. Patients with ALI/ARDS of less than 72 hours duration.
Stratification. Patients are prospectively stratified prior to randomization as (1) intubated
versus NPPV treated, and (2) ARDS versus severe ARDS. The purpose of stratification is to
distribute equally in both arms intubated versus NPPV treated, and ARDS versus severe ARDS.
End-points. The primary end-point of trial is 28 days all cause mortality; the secondary
end-points are (a) ventilator-free days at 28 days following study entry, (b) organ
failure-free days at 28 days following study entry, and (c) duration of ICU stay.