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

Acute Lung Injury Clinical Trial

Official title:

Simvastatin Effect on the Incidence of Acute Lung Injury/Adult Respiratory Distress Syndrome

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01195428
• Other study ID #: 15377
• Status: Withdrawn
• Phase: N/A
• First received: September 2, 2010
• Last updated: January 6, 2014
• Start date: October 2010
• Est. completion date: October 2011

Study information

• Verified date: January 2014
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Lung Injury
• Adult Respiratory Distress Syndrome
• Lung Injury
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Simvastatin
Simvastatin 40 mg daily
• Placebo
Placebo

Locations

Country	Name	City	State
United States	OU Medical Center	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
University of Oklahoma	VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of ARDS/ALI.		4 weeks	No