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

This study has been withdrawn prior to enrollment.
(Minimal enrollment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Oklahoma
ClinicalTrials.gov Identifier:
NCT01195428
First received: September 2, 2010
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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 Intervention
Adult Respiratory Distress Syndrome
Acute Lung Injury
Drug: Simvastatin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Simvastatin Effect on the Incidence of Acute Lung Injury/Adult Respiratory Distress Syndrome

Resource links provided by NLM:


Further study details as provided by University of Oklahoma:

Primary Outcome Measures:
  • Incidence of ARDS/ALI. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: October 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Simvastatin
Simvastatin 40 mg daily.
Drug: Simvastatin
Simvastatin 40 mg daily
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01195428

Locations
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
Investigators
Principal Investigator: Jean Keddissi, M.D. University of Oklahoma
Principal Investigator: Gary T. Kinasewitz, MD University of Oklahoma
  More Information

No publications provided

Responsible Party: University of Oklahoma
ClinicalTrials.gov Identifier: NCT01195428     History of Changes
Other Study ID Numbers: 15377
Study First Received: September 2, 2010
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 18, 2014