6-Methyl-Prednisolone for Multiple Organ Dysfunction Syndrome

• Status: Unknown status
• Trial end date: 2008-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Background: Systemic corticosteroids are considered in patients with an adverse clinical course suffering from conditions like the acute respiratory distress syndrome (ARDS) and septic shock. Treated patients not only show improved respiratory function, but also hemodynamic status and overall multiple organ dysfunction score.

Objective: To evaluate the safety and effectiveness of 6-methyl-prednisolone on the clinical course of multiple organ dysfunction syndrome (MODS).

Design: Multi-center, double-blind, randomized, placebo-controlled.

Intervention: Intravenous administration of 6-methyl-prednisolone or placebo (aqueous solution). The duration of the study medication administration protocol is 32 days (1).

Primary Endpoints:

1. All cause Intensive Care Unit (ICU) and 28-day mortality

2. Organ dysfunction score on days 4, 7, 14, and 28 of the protocol.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospital Universitario Principe de Asturias
• Collaborator: Pfizer
• Treatments: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:

Main Inclusion Criteria:

Patients with established, unresolving, refractory MODS, in whom all reversible and treatable causes of persistent MODS have been treated or ruled out:

• Patients under endotracheal intubation and mechanical ventilation for at least 7 days.

• Aggregate Multiple Organ Dysfunction Score (5) of greater than 8 over the first seven days of mechanical ventilation and greater than 5 on the day of inclusion.

• Written informed consent to participate in the trial signed by next of kin or other authorized person.

Additional Inclusion Criteria:

• Main cause or disease at admission: Adequate "source control" is required and refers to optimal, complete, and definitive surgical and/or medical therapy.

• Infections:

1. Infectious causes of persistence of MODS have reasonably been ruled out on clinical or other grounds (infectious endocarditis, undrained abscesses like sinusitis, empyema or abdominal pus). Consider sampling for culture of broncho-alveolar lavage fluid, protected specimen brush or other (empyema fluid, lung tissue) in order to rule out respiratory infection, as well as intra-vascular catheter change and culture.

2. Present or previous infections, either documented or strongly suspected, have been treated for at least 3 days before inclusion.

• Supportive Care: Optimal hemodynamic, renal, hematologic, nutritional "supportive care" is provided.

Exclusion Criteria:

• Decision not to provide full support.

• Immune status and steroid therapy.

1. Steroid therapy

• Currently indicated for chronic or concurrent disease (meningitis, auto-immune disease, asthma, acute exacerbation of chronic obstructive pulmonary disease [COPD], or other). Inhaled steroids are allowed.

• Administered during current admission (> 20 mg/day of 6-methyl-prednisolone or equivalent for >48 hours).

• Chronic steroid therapy prior to current admission (> 20 mg of 6-methyl-prednisolone or equivalent/day for > 1 month during previous 3 months).

2. Other immune-suppressive therapy within the previous 6 months.

3. Known AIDS.

4. Neutropenia < 500/mcl.

5. Preceding organ transplantation.

• Irreversible and or ultimately fatal clinical conditions like metastatic malignant disease or cardiogenic shock caused by coronary artery disease.

• Presence of invasive fungal infection

• Other significant pre-existing underlying chronic diseases:

1. Severe parenchymal liver disease (Child-Pugh grade C)

2. Severe and irreversible acute or chronic central nervous system disease.

3. Severe end-stage chronic obstructive pulmonary disease (home oxygen or more than 1 exacerbation in previous year)

4. End-stage renal disease (Chronic dialysis).

• Age less than 18 years.

• Pregnancy.

• Morbid obesity: body mass index above 40.

• Recent (last 3 months) upper gastrointestinal [GI] hemorrhage.

• Extensive burns (>30% body surface area [BSA])

• Known allergy to steroids.

• Written informed consent not available.