Steroids in Patients With Early ARDS

• Status: Unknown status
• Trial end date: 2009-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Catholic University of the Sacred Heart
• Treatments: Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Thiamine; Vitamin B Complex; Vitamins

Criteria

Inclusion Criteria:

• Age. Patients age 18 years or older admitted to the intensive care unit.

• ALI/ARDS criteria. The diagnosis of ALI/ARDS requires all of the following criteria:

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

• Acute onset of bilateral pulmonary densities on chest radiograph in the contest of appropriate predisposing injury or illness with no evidence of left ventricular failure,

• Static pulmonary compliance < 50 cm H2O

• Ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen (PaO2:FiO2 ) equal or less than 300 (criteria for ALI) or 200 (criteria for ARDS) with FiO2 1.0.

• Severe ARDS. PaO2:FiO2 equal or less than 200 after 30 minutes of standardized ventilatory management on PEEP of 10 cm H2O with FiO2 1.0.

Exclusion Criteria:

• Failure to obtain written informed consent from the patient or a next of kin.

• Trauma-induced ARDS.

• Major gastrointestinal bleeding requiring transfusion of 5 units or more of packed red blood cells (PRBC) within 3 months current hospitalization

• Condition requiring > 0.5mg/Kg/day of prednisone equivalent (i.e., acute asthma or chronic obstructive pulmonary disease [COPD])

• 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

• Pregnancy confirmed by urine or serum test

• Weight is > 200% of ideal body weight

• Non-ambulatory resident of long-term care facility

• Primary care physician not committed to full, aggressive support of the patient at the time of randomization

• Moribund patient (i.e., not expected to live more than 24 hr) or with recent (within 7 days or anytime during present hospitalization) cardiopulmonary arrest

• Known or suspected irreversible cessation of all brain function

• Presence of preexisting medical condition which is irreversible and expected to be fatal within 3 months

• 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)