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
  Purpose

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.


Condition Intervention Phase
Sepsis
Acute Lung Injury
Drug: Rosuvastatin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Trial of Rosuvastatin for Acutely Injured Lungs From Sepsis

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • The Primary efficacy measure is hospital mortality to day 60. [ Time Frame: 60 days after randomization ] [ Designated as safety issue: No ]

Enrollment: 745
Study Start Date: January 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rosuvastatin
Half of the subjects will receive the active drug, Rosuvastatin.
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
Placebo Comparator: Placebo
Half of the patients will be randomized to the placebo.
Drug: Placebo
Patients will receive one placebo by mouth or feeding tube daily for 28 days or until discharged form study hospital.

Detailed Description:

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.

  Eligibility

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

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
  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: NCT00979121

  Show 40 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Jonathon Truwit, MD University of Virginia, Medical Center
  More Information

Additional Information:
No publications provided by National Heart, Lung, and Blood Institute (NHLBI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00979121     History of Changes
Other Study ID Numbers: 670, N01HR056179
Study First Received: September 16, 2009
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
ALI
Sepsis
statin

Additional relevant MeSH terms:
Sepsis
Toxemia
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Lung Injury
Wounds and Injuries
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Thoracic Injuries
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014