Clinical Trial: 6-Methyl-Prednisolone for Multiple Organ Dysfunction Syndrome

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: The Effect of 6-Methyl-Prednisolone on Organ Dysfunction and Mortality of Patients With Unresolving Multiple Organ Dysfunction Syndrome

Brief 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.

Detailed Summary:

Background:

Worldwide intensive care physicians consider administering systemic corticosteroids in patients with an adverse clinical course suffering from conditions like the acute respiratory distress syndrome (ARDS) and septic shock. Data from recent small studies performed in patients with unresolving ARDS (1;2) suggest survival benefits associated with rescue therapy with relatively prolonged courses of corticosteroids. Treated patients not only show improved respiratory function, but also hemodynamic status and overall multiple organ dysfunction score. It has been suggested that that the integrity of the hypothalamic-pituitary-adrenal axis may be impaired in this patient subset (3;4)

Objective(s):

To evaluate the safety and effectiveness of a non-selective anti-inflammatory strategy, i.e. 6-methyl-prednisolone, on persistent and unresolving inflammatory states, i.e. multiple organ dysfunction syndrome, on the degree of organ dysfunction and mortality.

Design:

Multi-center, double-blind, randomized, placebo-controlled. Randomization and data entry is internet based (htpp://www.webnaif.com). Patients will be randomized through a computer-generated random-number table and stratified by center in blocs of 6. Sample size, by group 120 patients. The study is powered to detect a 20% reduction in mortality, from 50% to 30% in 100 patients per study group at the 5% significance level with a power of 80%. An additional 20% (n=20) per group have been planned to compensate for losses.

Main Inclusion Criteria:

  • Patients with established, unresolving, refr
    Sponsor: Hospital Universitario Principe de Asturias

    Current Primary Outcome:

    • All cause ICU and 28-day mortality [ Time Frame: 28 days ]
    • Organ dysfunction score on days 4, 7, 14, and 28 of the protocol [ Time Frame: Days 4, 7, 14, and 28. ]


    Original Primary Outcome:

    • 1. All cause ICU and 28-day mortality
    • 2. Organ dysfunction score on days 4, 7, 14, and 28 of the protocol.


    Current Secondary Outcome:

    • Mortality [ Time Frame: 28 days ]
    • Morbidity: Duration of mechanical ventilation and endotracheal intubation (also a surrogate for acute steroid myopathy) [ Time Frame: 28 days ]
    • Length of ICU-stay [ Time Frame: 28 days ]
    • Complications of steroid therapy [ Time Frame: 28 days ]
    • Infections acquired during the protocol [ Time Frame: 28 days ]
    • Other complications (hyperglycemia, GI bleeding, acute myopathy, pneumothorax) [ Time Frame: 28 days ]
    • Adrenal reserve as evaluated by adrenocorticotropic hormone (ACTH) test. [ Time Frame: Baseline ]


    Original Secondary Outcome:

    • 1. Mortality at 28 days.
    • 2. Morbidity
    • a. Duration of mechanical ventilation and endotracheal intubation (also a surrogate for acute steroid myopathy)
    • b. Length of ICU-stay
    • 3. Complications of steroid therapy
    • a. Infections acquired during the protocol
    • 2. Other complications (hyperglycemia, GI bleeding, acute myopathy, pneumothorax)
    • 4. Adrenal reserve as evaluated by ACTH test.


    Information By: Hospital Universitario Principe de Asturias

    Dates:
    Date Received: August 8, 2005
    Date Started: August 2005
    Date Completion: July 2008
    Last Updated: May 12, 2008
    Last Verified: May 2008