Simvastatin Effect on the Incidence of Acute Lung Injury/Adult Respiratory Distress Syndrome (ALI/ARDS)

Patients will be enrolled within 24 hours of ICU admission and randomized to 1 of 2 groups:
Simvastatin or placebo. Patients' management will be entirely left up to the primary team,
including the need for daily laboratory and imaging. In addition, there will be no
restriction on the use of any medications, as deemed necessary by the primary care
physician. The primary endpoint will be the incidence of ALI/ARDS. Secondary efficacy
variables will be the number of days without organ or system failure, in addition to the
change in IL-6, IL-8, and TNF- α. Treatment will continue until the primary endpoint is
reached, the patient discharged from the ICU or the maximum duration of 2 weeks, whichever
occurs first. Patients will continued to be followed for a total of 28 days, or until
discharged from the hospital, whichever occurs first.

Patients randomized, in a ratio of 1:1 to either Simvastatin 40 mg PO once daily or placebo
tablet once daily in a format identical to Simvastatin.

The mortality from ALI/ARDS remains significant. In the absence of effective therapy,
prophylaxis in patients at risk is an important goal to achieve. Therefore, if Simvastatin
is found to decrease the incidence of ALI/ARDS, it would be a significant advance in the
management of this deadly and frequent syndrome.

We have set up a Data Safety Monitoring Board (DSMB) that will closely monitor the progress
of the trial (DSMB Charter attached to this application). Any adverse event will be reported
directly to the institutional review board (IRB) and DSMB. All adverse events will be
reported in the annual review of the protocol.