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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01195428
Recruitment Status : Withdrawn (Minimal enrollment)
First Posted : September 6, 2010
Last Update Posted : January 7, 2014
VA Office of Research and Development
Information provided by (Responsible Party):
University of Oklahoma

Brief Summary:
Acute Lung Injury/Acute respiratory distress syndrome (ALI/ARDS) is a serious and frequently encountered entity in modern ICUs. Sepsis remains the most common cause of ALI/ARDS and carries the worst prognosis. The disease is characterized by an intense inflammatory process. This inflammation plays a major role in the development of gas exchange abnormalities seen in the course of the disease. Statins, primarily used as lipid-lowering agents, are now known to possess anti-inflammatory, antioxidant, antithrombogenic and vascular function-restoring actions. Therefore the investigators propose to determine if Simvastatin may be useful in decreasing the incidence of this deadly syndrome in critically ill patients.

Condition or disease Intervention/treatment Phase
Adult Respiratory Distress Syndrome Acute Lung Injury Drug: Simvastatin Drug: Placebo Not Applicable

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Simvastatin Effect on the Incidence of Acute Lung Injury/Adult Respiratory Distress Syndrome
Study Start Date : October 2010
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Arm Intervention/treatment
Active Comparator: Simvastatin
Simvastatin 40 mg daily.
Drug: Simvastatin
Simvastatin 40 mg daily

Placebo Comparator: Placebo
Drug: Placebo

Primary Outcome Measures :
  1. Incidence of ARDS/ALI. [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adults older than 18 years of age, admitted to the ICU with one or more of the following risk factors for ARDS/ALI:

    • Sepsis, defined as the presence of infection-related systemic inflammatory response syndrome (SIRS).

SIRS is defined as the presence of two or more of the following:

  • Temperature >38.5ºC or <35ºC
  • Heart rate >90 beats/min
  • Respiratory rate >20 breaths/min or PaCO2 <32 mmHg
  • WBC >12,000 cells/mm3, <4000 cells/mm3, or >10 percent immature (band) forms

    • Pneumonia, including community and health care associated pneumonias
    • Aspiration, defined as the witnessed inhalation of gastric contents
    • Acute pancreatitis
    • Bilateral lung contusion
    • Massive transfusion, defined as more than 15 units of red blood cells/24h
    • Multiple (>2) long-bone fractures

Exclusion Criteria:

  • Patients already on a statin
  • Current indication for statin therapy according to the National guidelines
  • NPO order
  • Active liver disease, defined as ALT or AST > 3 times the upper limits of normal
  • History of myopathy
  • History of uncontrolled seizure disorder
  • Pregnancy or breastfeeding
  • Immunosuppressive therapy, including prednisone at dose > 10 mg/day
  • Preexistent lung disease indicated by history or chest film
  • High risk for cardiogenic pulmonary edema (defined as the presence of ventricular fibrillation, acute myocardial infarction, congestive heart failure with EF < 40%)
  • High risk for neurogenic pulmonary edema (active CVA, or known increased intracranial pressure)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01195428

United States, Oklahoma
OU Medical Center
Oklahoma City, Oklahoma, United States, 73104
Veterans Affairs Medical Center
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
University of Oklahoma
VA Office of Research and Development
Principal Investigator: Jean Keddissi, M.D. University of Oklahoma
Principal Investigator: Gary T. Kinasewitz, MD University of Oklahoma

Responsible Party: University of Oklahoma Identifier: NCT01195428     History of Changes
Other Study ID Numbers: 15377
First Posted: September 6, 2010    Key Record Dates
Last Update Posted: January 7, 2014
Last Verified: January 2014

Additional relevant MeSH terms:
Wounds and Injuries
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Lung Injury
Acute Lung Injury
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors