SAILS: Statins for Acutely Injured Lungs From Sepsis

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00979121
• Collaborator: (none)
• Enrollment: 745
• Locations: 40
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 18.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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

Detailed Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 745 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized Trial of Rosuvastatin for Acutely Injured Lungs From Sepsis
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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: 28 days after randomization or 3 days after ICU discharge (whichever comes first), Discharge from study hospital, Death	Drug: Rosuvastatin; 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 Names: 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.	Drug: Placebo; Subjects received placebo by mouth or feeding tube daily for 28 days or until discharged from study hospital.

Outcome Measures

Primary Outcome Measures

1. Hospital Mortality to Day 60. [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.

Secondary Outcome Measures

1. Ventilator Free Days at Study Day 28 [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.

Other Outcome Measures

1. Organ Failure Free Days at Day 14 [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.

2. ICU Free Days to Day 28 [28 days after randomization]

3. Other Secondary Out-comes [28 days after randomization]

   Percentage of subjects with Arrhythmia's, Bowel Ischemia, Myocardial Infarction, Ischemic Stroke, and Thromboembolism were measured.

4. Changes in Plasma Concentrations of C-reactive Protein (CRP) From Baseline to Day 6 and Day 14 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 >38 degrees Celsius (C) (any route) or <36 degrees C (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).

4. ALI as defined by acute onset of:

5. PaO2 / FiO2 ≤ 300 (intubated). If altitude > 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760), and

6. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and

7. Requirement for positive pressure ventilation via an endotracheal tube, and

8. 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

• 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

1. Severe chronic liver disease

2. Moribund patient not expected to survive 24 hours

3. Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting

4. 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

5. Diffuse alveolar hemorrhage from vasculitis

6. Burns > 40% total body surface

7. Interstitial lung disease of severity sufficient to require continuous home oxygen therapy

8. Unwillingness or inability to utilize the ARDS network 6 ml/kg Predicted Body Weight (PBW) ventilation protocol

9. Cardiac disease classified as NYHA (New York Heart Association) class IV

10. Myocardial infarction within past 6 months

11. Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization.

12. Temperature >40.3 C in the 6 hours before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of San Francisco-Fresno Medical Center	Fresno	California	United States
2	University of California, Davis Medical Center	Sacramento	California	United States
3	UCSF-Moffitt Hospital	San Francisco	California	United States
4	University of California, San Francisco (UCSF)-Moffitt Hospital	San Francisco	California	United States
5	Centura St. Anthony Central Hospital	Denver	Colorado	United States
6	Denver Health Medical Center	Denver	Colorado	United States
7	Rose Medical Center	Denver	Colorado	United States
8	University of Colorado Health Sciences Center	Denver	Colorado	United States
9	Washington Hospital Center	Washington DC	District of Columbia	United States
10	Baton Rouge General Hospital-Blue Bonnet	Baton Rouge	Louisiana	United States
11	Baton Rouge General Hospital-Midcity	Baton Rouge	Louisiana	United States
12	Earl K. Long Medical Center	Baton Rouge	Louisiana	United States
13	Our Lady of the Lake Regional Medical Center	Baton Rouge	Louisiana	United States
14	Medical Center of Louisiana	New Orleans	Louisiana	United States
15	Ochsner Clinic Foundation	New Orleans	Louisiana	United States
16	Tulane University Health Sciences Center	New Orleans	Louisiana	United States
17	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States
18	Johns Hopkins Hospital	Baltimore	Maryland	United States
19	University of Maryland Shock Trauma Center	Baltimore	Maryland	United States
20	Baystate Medical Center	Springfield	Massachusetts	United States
21	Rochester Methodist Hospital	Rochester	Minnesota	United States
22	St. Mary's Hospital, Mayo Clinic	Rochester	Minnesota	United States
23	Duke University Medical Center	Durham	North Carolina	United States
24	Durham Regional Medical Center	Durham	North Carolina	United States
25	Moses Cone Health System	Greensboro	North Carolina	United States
26	Wesley Long Community Hospital	Greensboro	North Carolina	United States
27	Wake Forest University Baptist Medical Center	Winston Salem	North Carolina	United States
28	Cleveland Clinic Foundation	Cleveland	Ohio	United States
29	MetroHealth Medical Center	Cleveland	Ohio	United States
30	University Hospitals of Cleveland	Cleveland	Ohio	United States
31	Vanderbilt University Medical Center	Nashville	Tennessee	United States
32	Baylor College of Medicine	Houston	Texas	United States
33	Intermountain Medical Center	Murray	Utah	United States
34	McKay-Dee Hospital	Ogden	Utah	United States
35	Utah Valley Regional Medical Center	Provo	Utah	United States
36	LDS Hospital	Salt Lake City	Utah	United States
37	University of Virginia Medical Center	Charlottesville	Virginia	United States
38	Providence Hospital	Everett	Washington	United States	98201
39	Harborview Medical Center	Seattle	Washington	United States
40	University of Washington	Seattle	Washington	United States

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: Jonathon Truwit, MD, University of Virginia, Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• ARDS Network Website

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00979121
• Other Study ID Numbers: 670; N01HR056179
• First Posted: Sep 17, 2009
• Last Update Posted: May 16, 2016
• Last Verified: Aug 1, 2014

• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): ALI; Sepsis; statin
• Additional relevant MeSH terms: Sepsis; Toxemia; Lung Injury; Acute Lung Injury; Rosuvastatin Calcium

Study Results

Participant Flow

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects will receive the active drug, Rosuvastatin. 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.	Half of the patients will be randomized to the placebo. Placebo: Patients will receive one placebo by mouth or feeding tube daily for 28 days or until discharged form study hospital.
Period Title: Overall Study
STARTED	379	366
COMPLETED	379	366
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Rosuvastatin	Placebo	Total
Arm/Group Description	Half of the subjects will receive the active drug, Rosuvastatin. 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.	Half of the patients will be randomized to the placebo. Placebo: Patients will receive one placebo by mouth or feeding tube daily for 28 days or until discharged form study hospital.	Total of all reporting groups
Overall Participants	379	366	745
Age (Count of Participants)
<=18 years	3 0.8%	2 0.5%	5 0.7%
Between 18 and 65 years	262 69.1%	272 74.3%	534 71.7%
>=65 years	114 30.1%	92 25.1%	206 27.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.2 (17.1)	54.1 (15.6)	54.1 (16.3)
Sex: Female, Male (Count of Participants)
Female	195 51.5%	185 50.5%	380 51%
Male	184 48.5%	181 49.5%	365 49%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	46 12.1%	40 10.9%	86 11.5%
Not Hispanic or Latino	333 87.9%	326 89.1%	659 88.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (participants) [Number]
American Indian or Alaska Native	1 0.3%	5 1.4%	6 0.8%
Asian	9 2.4%	7 1.9%	16 2.1%
Native Hawaiian or Other Pacific Islander	2 0.5%	3 0.8%	5 0.7%
Black or African American	52 13.7%	53 14.5%	105 14.1%
White	289 76.3%	301 82.2%	590 79.2%
More than one race	NA NaN	NA NaN	NA NaN
Unknown or Not Reported	14 3.7%	10 2.7%	24 3.2%
Region of Enrollment (participants) [Number]
United States	379 100%	366 100%	745 100%
APACHE III Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	92.1 (28.4)	94.8 (27.9)	93.4 (28.2)
Primary cause of lung injury (participants) [Number]
Aspiration	26 6.9%	23 6.3%	49 6.6%
Multiple Transfusion	3 0.8%	1 0.3%	4 0.5%
Other	7 1.8%	4 1.1%	11 1.5%
Pneumonia	267 70.4%	260 71%	527 70.7%
Sepsis	72 19%	73 19.9%	145 19.5%
Trauma	2 0.5%	4 1.1%	6 0.8%
Baseline Shock (participants) [Number]
Number [participants]	173 45.6%	166 45.4%	339 45.5%
PaFiO2:FiO2 ratio less than or equal to 200 mm Hg (participants) [Number]
Number [participants]	267 70.4%	253 69.1%	520 69.8%
Hours from intubation to randomization (participants) [Number]
24 hours or less	124 32.7%	129 35.2%	253 34%
between 24 and 48 hours	204 53.8%	192 52.5%	396 53.2%
between 48 and 72 hours	41 10.8%	31 8.5%	72 9.7%
more than 72 hours	10 2.6%	13 3.6%	23 3.1%
Unknown	0 0%	1 0.3%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Hospital Mortality to Day 60.
Description	The percentage of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.
Time Frame	60 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects were randomized to active drug (Rosuvastatin). Rosuvastatin: Subjects received 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharge from the study hospital.	Half of the subjects were randomized to placebo. Placebo: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharge from study hospital.
Measure Participants	379	366
Number (95% Confidence Interval) [percentage of participants]	28.5 7.5%	24.9 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin, Placebo
	Comments	Hospital mortality to day 60 was estimated using the Kaplan Meier estimate, with patients discharged home before day 60 considered alive at day 60. The analysis was stratified by co-enrolled treatment assignments for 81 patients also enrolled in a randomized clinical trial of two different nutritional strategies. A maximum of 1000 patients were to be enrolled, providing a 92% probability of rejecting the null hypothesis for the effect on mortality if a true difference in mortality was 9%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments	The monitoring boundaries were designed to have a low probability of stopping for futility before 750 patients. The maximum sample size was 1000 patients. Efficacy stopping was based on mortality; futility stopping was based on mortality and VFDs.
	Method	Proc lifetest
	Comments	Proc lifetest was used to calculate mortality mean and variance due to one subject lost to follow up who was censored.
Method of Estimation	Estimation Parameter	difference in % of pts alive at 60 days
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; -2.3 to 10.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Ventilator Free Days at Study Day 28
Description	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.
Time Frame	time of initiating unassisted breathing to day 28 after study randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects were randomized to active drug (Rosuvastatin). Rosuvastatin: Subjects received 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharge from the study hospital.	Half of the subjects were randomized to placebo. Placebo: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharged from study hospital.
Measure Participants	379	366
Mean (Standard Deviation) [days]	15.1 (10.8)	15.1 (11.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin, Placebo
	Comments	Ventilator, ICU free, and organ failure free days were analyzed by analysis of variance, utilizing treatment assignment where applicable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	() 95%; -1.6 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	Organ Failure Free Days at Day 14
Description	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.
Time Frame	14 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects were randomized to active drug (Rosuvastatin). Rosuvastatin: Patients received 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharge from the study hospital.	Half of the subjects were randomized to placebo. Placebo: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharge from study hospital.
Measure Participants	379	366
Cardiovascular	8.5 (4.8)	8.7 (4.9)
Coagulation	10.7 (5.1)	11.1 (4.8)
Hepatic	10.8 (5.0)	11.8 (4.3)
Renal	10.1 (5.3)	11.0 (4.7)

4. Other Pre-specified Outcome

Title	ICU Free Days to Day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects will receive the active drug, Rosuvastatin. 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.	Half of the patients will be randomized to the placebo. Placebo: Patients will receive one placebo by mouth or feeding tube daily for 28 days or until discharged form study hospital.
Measure Participants	379	366
Mean (Standard Deviation) [days]	14.3 (10.1)	14.4 (10.3)

5. Other Pre-specified Outcome

Title	Other Secondary Out-comes
Description	Percentage of subjects with Arrhythmia's, Bowel Ischemia, Myocardial Infarction, Ischemic Stroke, and Thromboembolism were measured.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects were randomized to active drug (Rosuvastatin). Rosuvastatin: Subjects received 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharge from the study hospital.	Half of the subjects were randomized to placebo. Placebo: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharge from study hospital.
Measure Participants	367	360
Arrhythmias	9.0 2.4%	8.4 2.3%
Bowel Ischemia	1.4 0.4%	1.9 0.5%
Myocardial Infarction	0.5 0.1%	0.6 0.2%
Ischemic Stroke	0.3 0.1%	0.3 0.1%
Thromboembolism	6.3 1.7%	6.9 1.9%

6. Other Pre-specified Outcome

Title	Changes in Plasma Concentrations of C-reactive Protein (CRP) From Baseline to Day 6 and Day 14
Description	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.
Time Frame	6 and 14 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin	Placebo
Arm/Group Description	Half of the subjects were randomized to active drug (Rosuvastatin). Rosuvastatin:Subjects received 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharge from the study hospital.	Half of the subjects were randomized to placebo. Placebo: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharge from study hospital.
Measure Participants	229	229
Day 6	-12.9 (27.79)	-15.1 (23.26)
Day 14	-19.8 (31.23)	-14.8 (26.28)

Adverse Events

Time Frame	Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.
Adverse Event Reporting Description	AE definition: any clinically important untoward medical occurrence in a patient receiving study drug/procedures which was different than expected in the clinical course of a patient with ALI or an occurrence thought to be associated with the study drug/procedures. CK, ALT/AST at specified levels and CNS bleed were also systematically reported.
Arm/Group Title	Rosuvastatin		Placebo
Arm/Group Description	Half of the subjects were randomized to the active drug (Rosuvastatin). Rosuvastatin: Subjects received 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharge from the study hospital.		Half of the subjects were randomized to placebo. Placebo: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharge from study hospital.
All Cause Mortality
	Rosuvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rosuvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/379 (9%)		32/366 (8.7%)
Blood and lymphatic system disorders
Pancytopenia	0/379 (0%)	0	1/366 (0.3%)	1
Thrombocytopenia	0/379 (0%)	0	1/366 (0.3%)	1
Cardiac disorders
Asystole	0/379 (0%)	0	1/366 (0.3%)	1
Cardiac Arrest	3/379 (0.8%)	3	4/366 (1.1%)	4
Cardiopulmonary Arrest	0/379 (0%)	0	1/366 (0.3%)	1
Hemorrhage (Nos)	1/379 (0.3%)	1	0/366 (0%)	0
Thrombosis Venous Arm	1/379 (0.3%)	1	0/366 (0%)	0
Venous Thrombosis	1/379 (0.3%)	1	1/366 (0.3%)	1
Gastrointestinal disorders
ALT > 8 times upper limit of normal	0/379 (0%)	0	3/366 (0.8%)	3
Bowel Perforation	0/379 (0%)	0	1/366 (0.3%)	1
Gastrointestinal Bleeding	1/379 (0.3%)	1	0/366 (0%)	0
Ischemia Bowel	0/379 (0%)	0	1/366 (0.3%)	1
Necrosis Bowel	1/379 (0.3%)	1	0/366 (0%)	0
Obstruction Small Intestine	1/379 (0.3%)	1	0/366 (0%)	0
Peforation Bowel	0/379 (0%)	0	1/366 (0.3%)	1
Proctitis	1/379 (0.3%)	1	0/366 (0%)	0
General disorders
Hemorrhage Retroperitoneal	1/379 (0.3%)	1	1/366 (0.3%)	1
Hyperpyrexia	2/379 (0.5%)	2	0/366 (0%)	0
Necrosis	0/379 (0%)	0	1/366 (0.3%)	1
Neuroleptic Malignant Syndrome	1/379 (0.3%)	1	0/366 (0%)	0
Investigations
AST > 8 times upper limit of normal	2/379 (0.5%)	2	0/366 (0%)	0
Aspartate Aminotransferase Increased	1/379 (0.3%)	1	0/366 (0%)	0
Ast Increased	1/379 (0.3%)	1	0/366 (0%)	0
Creatinine Serum Increased	0/379 (0%)	0	1/366 (0.3%)	1
Musculoskeletal and connective tissue disorders
CK > 10 times upper limit of normal	4/379 (1.1%)	4	4/366 (1.1%)	4
Rhabdomyolysis	1/379 (0.3%)	1	0/366 (0%)	0
Nervous system disorders
Agitation	1/379 (0.3%)	1	0/366 (0%)	0
Brain Disorder (Nos)	0/379 (0%)	0	1/366 (0.3%)	1
Cognitive Disturbance	0/379 (0%)	0	1/366 (0.3%)	1
Delirium	1/379 (0.3%)	1	0/366 (0%)	0
Encephalopathy	0/379 (0%)	0	1/366 (0.3%)	1
Intracerebral Hemorrhage	1/379 (0.3%)	1	0/366 (0%)	0
Stroke	2/379 (0.5%)	2	0/366 (0%)	0
Renal and urinary disorders
Failure Kidney Acute	1/379 (0.3%)	1	0/366 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/379 (0.3%)	1	0/366 (0%)	0
Aspiration	1/379 (0.3%)	1	1/366 (0.3%)	1
Coughing Blood	0/379 (0%)	0	1/366 (0.3%)	1
Embolism Pulmonary	2/379 (0.5%)	2	2/366 (0.5%)	2
Hypoxemia	0/379 (0%)	0	1/366 (0.3%)	1
Pleural Effusion	1/379 (0.3%)	1	0/366 (0%)	0
Pneumothorax	0/379 (0%)	0	1/366 (0.3%)	1
Skin and subcutaneous tissue disorders
Skin Ulceration	0/379 (0%)	0	1/366 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Rosuvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/379 (0%)		0/366 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

sponsor can review results communications prior to public release and can embargo communications regarding trial results until presented at the American Thoracic Society international meeting.