Trial record 1 of 10 for:    SAILS
Previous Study | Return to List | Next Study

Statins for Acutely Injured Lungs From Sepsis (SAILS)

This study has been terminated.
(stopped for futility)
Sponsor:
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00979121
First received: September 16, 2009
Last updated: October 18, 2013
Last verified: October 2013

September 16, 2009
October 18, 2013
January 2010
November 2013   (final data collection date for primary outcome measure)
The Primary efficacy measure is hospital mortality to day 60. [ Time Frame: 60 days after randomization ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00979121 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Statins for Acutely Injured Lungs From Sepsis
Randomized Trial of Rosuvastatin for Acutely Injured Lungs From Sepsis

The objective is to assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced Acute Lung Injury (ALI). The hypothesis of this study is that Rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.

ALI/ARDS involves extensive inflammation in the lungs that can lead to rapid respiratory failure. These conditions are most commonly caused by pneumonia, generalized infection, or severe trauma to the lungs, but can also be less commonly caused by smoke or salt water inhalation, drug overdose, or shock.

For some people, ALI/ARDS resolves without treatment, but many severe cases result in hospitalization in the intensive care unit (ICU), where 30% to 40% of cases end in mortality. Current treatments for ALI/ARDS include assisted breathing with a ventilator, supportive care, and management of the underlying causes.

Upon admission to the ICU, Rosuvastatin or placebo will be administered through an enteral feeding tube or administered orally following extubation when patients are able to safely take oral medications. The type and placement of the enteral feeding tube (nasogastric, nasoenteric, PEG, orogastric, oroenteric, etc.) and the ability to safely take oral medications will be determined by the patient's primary team. Study drug will be blinded with an identical appearing placebo. The first study drug dose (rosuvastatin or placebo) will be administered within 4 hours of randomization as a loading dose of 40 mg.

Blood pressure, heart rate, ventilation settings, and various blood factors will be measured during treatment. Phone-based follow-up assessments will occur at Months 6 and 12 after ICU discharge and will include measurements of health-related quality of life; psychological, neurocognitive, and physical activity outcomes; healthcare utilization; and mortality.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Sepsis
  • Acute Lung Injury
  • Drug: Rosuvastatin
    Patients will receive 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharged from the study hospital.
    Other Name: Crestor
  • Drug: Placebo
    Patients will receive one placebo by mouth or feeding tube daily for 28 days or until discharged form study hospital.
  • Active Comparator: Rosuvastatin
    Half of the subjects will receive the active drug, Rosuvastatin.
    Intervention: Drug: Rosuvastatin
  • Placebo Comparator: Placebo
    Half of the patients will be randomized to the placebo.
    Intervention: Drug: Placebo
National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
745
November 2013
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 1. Systemic inflammatory response syndrome (SIRS) defined as meeting at least criteria (a) or (b)for a systemic inflammatory response:

    1. White blood cell count >12,000 or <4,000 or >10% band forms
    2. Body temperature >38oC (any route) or <36oC (accepting core temperatures only; indwelling catheter, esophageal, rectal)
    3. Heart rate (> 90 beats/min) or receiving medications that slow heart rate or paced rhythm 2. Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and bacterial meningitis (Appendix A).

      3. ALI as defined by acute onset of:

    1. PaO2 / FiO2 ≤ 300 (intubated). If altitude > 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760), and
    2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and
    3. Requirement for positive pressure ventilation via an endotracheal tube, and
    4. No clinical evidence of left atrial hypertension, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mm Hg. If a patient has a PAOP > 18 mmHg, then the other criteria must persist for more than 12 hours after the PAOP has declined to ≤ 18 mmHg, and still be within the 48-hour enrollment window.

"Acute onset" is defined as follows: the duration of the hypoxemia criterion (#1) and the chest radiograph criterion (#2) must be ≤ 28 days at the time of randomization. Opacities considered "consistent with pulmonary edema" include any patchy or diffuse opacities not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (> 28 days). The findings of vascular redistribution, indistinct vessels, and indistinct cardiac borders are not considered "consistent with pulmonary edema".

All ALI criteria (3a-d above) must occur within the same 24 hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset and no more than 7 days from the initiation of mechanical ventilation. SIRS criteria must occur within the 72 hours before or the 24 hours after ALI onset. Information for determining when these time window criteria were met may come from either the Network hospital or a referring hospital reports.

Exclusion Criteria:

  1. No consent/inability to obtain consent
  2. Age less than 18 years
  3. More than 7 days since initiation of mechanical ventilation
  4. More than 48 hours since meeting ALI inclusion criteria
  5. Patient, surrogate, or physician not committed to full support ).
  6. Unable to receive or unlikely to absorb enteral study drug
  7. Rosuvastatin specific exclusions

    • Receiving a statin medication within 48 hours of randomization
    • Allergy or intolerance to statins
    • Physician insistence for the use or avoidance of statins during the current hospitalization
    • CK , ALT or AST > 5 times the upper limit of normal
    • Diagnosis of hypothyroidism and not on thyroid replacement therapy
    • Pregnancy or breast feeding
    • Receiving niacin, fenofibrate or cyclosporine, gemfibrozil, atazanavir, lopinavir, ritonavir, daptomycin
  8. Severe chronic liver disease
  9. Moribund patient not expected to survive 24 hours
  10. Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting
  11. Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
  12. Diffuse alveolar hemorrhage from vasculitis
  13. Burns > 40% total body surface
  14. Interstitial lung disease of severity sufficient to require continuous home oxygen therapy
  15. Unwillingness or inability to utilize the ARDS network 6 ml/kg PBW ventilation protocol
  16. Cardiac disease classified as NYHA class IV
  17. Myocardial infarction within past 6 months
  18. Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization.
  19. Temperature >40.3 C in the 6 hours before randomization
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00979121
670, N01HR056179
Yes
National Heart, Lung, and Blood Institute (NHLBI)
National Heart, Lung, and Blood Institute (NHLBI)
Not Provided
Study Chair: Jonathon Truwit, MD University of Virginia, Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP