Statins for Acutely Injured Lungs From Sepsis (SAILS)
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|ClinicalTrials.gov Identifier: NCT00979121|
Recruitment Status : Terminated (stopped for futility)
First Posted : September 17, 2009
Results First Posted : October 3, 2014
Last Update Posted : May 16, 2016
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Objective: assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced Acute Lung Injury (ALI).
Hypothesis: Rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.
|Condition or disease||Intervention/treatment||Phase|
|Sepsis Acute Lung Injury||Drug: Rosuvastatin Drug: Placebo||Phase 3|
Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (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 was administered through an enteral feeding tube or administered orally following extubation when patients were 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 was determined by the patient's primary team. Study drug was blinded with an identical appearing placebo. The first study drug dose (rosuvastatin or placebo) was administered within 4 hours of randomization as a loading dose of 40 mg.
Blood pressure, heart rate, ventilation settings, and various blood factors were measured during treatment. Phone-based follow-up assessments occurred at months 6 and 12 after ICU discharge and included measurements of health-related quality of life; psychological, neurocognitive, and physical activity outcomes; healthcare utilization; and mortality.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||745 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Randomized Trial of Rosuvastatin for Acutely Injured Lungs From Sepsis|
|Study Start Date :||January 2010|
|Actual Primary Completion Date :||November 2013|
|Actual Study Completion Date :||November 2013|
Active Comparator: Rosuvastatin
Half of the subjects were randomized to the active drug (Rosuvastatin).
Dosage, Form, and Frequency: drug was provided as 10mg tablets and administered through an enteral feeding tube or orally (following extubation when patients were able to safely take oral medications). An initial 40mg loading dose was administered followed by a daily 20 mg maintenance dose. Maintenance dosing was adjusted for renal failure not compensated by renal replacement therapy.
Duration: drug was administered daily until:
Subjects received an initial 40mg loading dose followed by 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 subjects were randomized to placebo.
10mg tablets identical to active drug were administered through an enteral feeding tube or orally (following extubation when patients were able to safely take oral medications). Dosage, frequency, and duration was provided in the same manner as the active drug.
Subjects received placebo by mouth or feeding tube daily for 28 days or until discharged from study hospital.
- Hospital Mortality to Day 60. [ Time Frame: 60 days after randomization ]The percentage of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.
- Ventilator Free Days at Study Day 28 [ Time Frame: time of initiating unassisted breathing to day 28 after study randomization ]Ventilator Free Days (VFDs) to day 28 were defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject received assisted breathing at day 27 or died prior to day 28, a value of zero VFDs was given.
- Organ Failure Free Days at Day 14 [ Time Frame: 14 days after randomization ]The number of days from randomization to day 14 without an organ failure. Four main organ systems were measured: cardiovascular, coagulation, hepatic function, and renal function.
- ICU Free Days to Day 28 [ Time Frame: 28 days after randomization ]
- Other Secondary Out-comes [ Time Frame: 28 days after randomization ]Percentage of subjects with Arrhythmia's, Bowel Ischemia, Myocardial Infarction, Ischemic Stroke, and Thromboembolism were measured.
- Changes in Plasma Concentrations of C-reactive Protein (CRP) From Baseline to Day 6 and Day 14 [ Time Frame: 6 and 14 days after randomization ]CRP levels were collected on subjects at baseline and on-study. The change in concentration from baseline levels to levels on study days 6 and 14 was analyzed. Those subjects that were still alive and on study at day 6 and 14 with a measured CRP level were included in the analysis.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
1. Systemic inflammatory response syndrome (SIRS) defined as meeting at least criteria (a) or (b)for a systemic inflammatory response:
- White blood cell count >12,000 or <4,000 or >10% band forms
- Body temperature >38 degrees Celsius (C) (any route) or <36 degrees C (accepting core temperatures only; indwelling catheter, esophageal, rectal)
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:
- PaO2 / FiO2 ≤ 300 (intubated). If altitude > 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760), and
- Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and
- Requirement for positive pressure ventilation via an endotracheal tube, and
- 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.
- No consent/inability to obtain consent
- Age less than 18 years
- More than 7 days since initiation of mechanical ventilation
- More than 48 hours since meeting ALI inclusion criteria
- Patient, surrogate, or physician not committed to full support ).
- Unable to receive or unlikely to absorb enteral study drug
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
- Creatine Kinase (CK) , alanine aminotransferase (ALT) or aspartate aminotransferase (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
- Severe chronic liver disease
- Moribund patient not expected to survive 24 hours
- Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting
- Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP/BIPAP (Continuous Positive Airway Pressure/BiLevel Positive Airway Pressure) used solely for sleep-disordered breathing
- Diffuse alveolar hemorrhage from vasculitis
- Burns > 40% total body surface
- Interstitial lung disease of severity sufficient to require continuous home oxygen therapy
- Unwillingness or inability to utilize the ARDS network 6 ml/kg Predicted Body Weight (PBW) ventilation protocol
- Cardiac disease classified as NYHA (New York Heart Association) class IV
- Myocardial infarction within past 6 months
- Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization.
- Temperature >40.3 C in the 6 hours before randomization
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 ClinicalTrials.gov identifier (NCT number): NCT00979121
|Study Chair:||Jonathon Truwit, MD||University of Virginia, Medical Center|
Study Data/Documents: Individual Participant Data Set
NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||National Heart, Lung, and Blood Institute (NHLBI)|
|Other Study ID Numbers:||
N01HR056179 ( Other Grant/Funding Number: NHLBI )
|First Posted:||September 17, 2009 Key Record Dates|
|Results First Posted:||October 3, 2014|
|Last Update Posted:||May 16, 2016|
|Last Verified:||August 2014|
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