Trial Outcomes & Findings for Statins for Acutely Injured Lungs From Sepsis (NCT NCT00979121)

Last Updated: 2016-05-16

Results Overview

The percentage of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

745 participants

Primary outcome timeframe

60 days after randomization

Results posted on

2016-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	Rosuvastatin 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.	Placebo 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.
Overall Study STARTED	379	366
Overall Study COMPLETED	379	366
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Statins for Acutely Injured Lungs From Sepsis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rosuvastatin n=379 Participants 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.	Placebo n=366 Participants 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 n=745 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	262 Participants n=5 Participants	272 Participants n=7 Participants	534 Participants n=5 Participants
Age, Categorical >=65 years	114 Participants n=5 Participants	92 Participants n=7 Participants	206 Participants n=5 Participants
Age, Continuous	54.2 years STANDARD_DEVIATION 17.1 • n=5 Participants	54.1 years STANDARD_DEVIATION 15.6 • n=7 Participants	54.1 years STANDARD_DEVIATION 16.3 • n=5 Participants
Sex: Female, Male Female	195 Participants n=5 Participants	185 Participants n=7 Participants	380 Participants n=5 Participants
Sex: Female, Male Male	184 Participants n=5 Participants	181 Participants n=7 Participants	365 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	46 Participants n=5 Participants	40 Participants n=7 Participants	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	333 Participants n=5 Participants	326 Participants n=7 Participants	659 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants
Race (NIH/OMB) Asian	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Race (NIH/OMB) Black or African American	52 participants n=5 Participants	53 participants n=7 Participants	105 participants n=5 Participants
Race (NIH/OMB) White	289 participants n=5 Participants	301 participants n=7 Participants	590 participants n=5 Participants
Race (NIH/OMB) More than one race	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 participants n=5 Participants	10 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment United States	379 participants n=5 Participants	366 participants n=7 Participants	745 participants n=5 Participants
APACHE III Score	92.1 units on a scale STANDARD_DEVIATION 28.4 • n=5 Participants	94.8 units on a scale STANDARD_DEVIATION 27.9 • n=7 Participants	93.4 units on a scale STANDARD_DEVIATION 28.2 • n=5 Participants
Primary cause of lung injury Aspiration	26 participants n=5 Participants	23 participants n=7 Participants	49 participants n=5 Participants
Primary cause of lung injury Multiple Transfusion	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Primary cause of lung injury Other	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants
Primary cause of lung injury Pneumonia	267 participants n=5 Participants	260 participants n=7 Participants	527 participants n=5 Participants
Primary cause of lung injury Sepsis	72 participants n=5 Participants	73 participants n=7 Participants	145 participants n=5 Participants
Primary cause of lung injury Trauma	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Baseline Shock	173 participants n=5 Participants	166 participants n=7 Participants	339 participants n=5 Participants
PaFiO2:FiO2 ratio less than or equal to 200 mm Hg	267 participants n=5 Participants	253 participants n=7 Participants	520 participants n=5 Participants
Hours from intubation to randomization 24 hours or less	124 participants n=5 Participants	129 participants n=7 Participants	253 participants n=5 Participants
Hours from intubation to randomization between 24 and 48 hours	204 participants n=5 Participants	192 participants n=7 Participants	396 participants n=5 Participants
Hours from intubation to randomization between 48 and 72 hours	41 participants n=5 Participants	31 participants n=7 Participants	72 participants n=5 Participants
Hours from intubation to randomization more than 72 hours	10 participants n=5 Participants	13 participants n=7 Participants	23 participants n=5 Participants
Hours from intubation to randomization Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rosuvastatin n=379 Participants 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.	Placebo n=366 Participants 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.
Hospital Mortality to Day 60.	28.5 percentage of participants Interval 24.0 to 33.0	24.9 percentage of participants Interval 20.5 to 29.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rosuvastatin n=379 Participants 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.	Placebo n=366 Participants 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.
Ventilator Free Days at Study Day 28	15.1 days Standard Deviation 10.8	15.1 days Standard Deviation 11.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rosuvastatin n=379 Participants 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.	Placebo n=366 Participants 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.
Organ Failure Free Days at Day 14 Cardiovascular	8.5 days Standard Deviation 4.8	8.7 days Standard Deviation 4.9
Organ Failure Free Days at Day 14 Coagulation	10.7 days Standard Deviation 5.1	11.1 days Standard Deviation 4.8
Organ Failure Free Days at Day 14 Hepatic	10.8 days Standard Deviation 5.0	11.8 days Standard Deviation 4.3
Organ Failure Free Days at Day 14 Renal	10.1 days Standard Deviation 5.3	11.0 days Standard Deviation 4.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

Outcome measures

Outcome measures
Measure	Rosuvastatin n=379 Participants 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.	Placebo n=366 Participants 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.
ICU Free Days to Day 28	14.3 days Standard Deviation 10.1	14.4 days Standard Deviation 10.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

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

Outcome measures

Outcome measures
Measure	Rosuvastatin n=367 Participants 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.	Placebo n=360 Participants 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.
Other Secondary Out-comes Ischemic Stroke	0.3 percentage of participants Interval -0.03 to 0.9	0.3 percentage of participants Interval -0.3 to 0.9
Other Secondary Out-comes Arrhythmias	9.0 percentage of participants Interval 6.1 to 11.9	8.4 percentage of participants Interval 5.5 to 11.3
Other Secondary Out-comes Bowel Ischemia	1.4 percentage of participants Interval 0.2 to 2.6	1.9 percentage of participants Interval 0.5 to 3.3
Other Secondary Out-comes Myocardial Infarction	0.5 percentage of participants Interval -0.3 to 1.3	0.6 percentage of participants Interval -0.2 to 1.4
Other Secondary Out-comes Thromboembolism	6.3 percentage of participants Interval 3.8 to 8.9	6.9 percentage of participants Interval 4.4 to 9.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rosuvastatin n=229 Participants 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.	Placebo n=229 Participants 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.
Changes in Plasma Concentrations of C-reactive Protein (CRP) From Baseline to Day 6 and Day 14 Day 6	-12.9 mg/dL Standard Deviation 27.79	-15.1 mg/dL Standard Deviation 23.26
Changes in Plasma Concentrations of C-reactive Protein (CRP) From Baseline to Day 6 and Day 14 Day 14	-19.8 mg/dL Standard Deviation 31.23	-14.8 mg/dL Standard Deviation 26.28

Adverse Events

Rosuvastatin

Serious events: 34 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 32 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

David A. Schoenfeld, PhD ARDSNet CCC PI

ARDS Network

Phone: 617-726-6111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Rosuvastatin n=379 participants at risk 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.	Placebo n=366 participants at risk 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.
General disorders Hemorrhage Retroperitoneal	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
General disorders Hyperpyrexia	0.53% 2/379 • Number of events 2 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
General disorders Necrosis	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
General disorders Neuroleptic Malignant Syndrome	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Cardiac disorders Asystole	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Cardiac disorders Cardiac Arrest	0.79% 3/379 • Number of events 3 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	1.1% 4/366 • Number of events 4 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Cardiac disorders Cardiopulmonary Arrest	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Cardiac disorders Hemorrhage (Nos)	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Cardiac disorders Thrombosis Venous Arm	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Cardiac disorders Venous Thrombosis	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders ALT > 8 times upper limit of normal	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.82% 3/366 • Number of events 3 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Bowel Perforation	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Gastrointestinal Bleeding	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Ischemia Bowel	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Necrosis Bowel	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Obstruction Small Intestine	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Peforation Bowel	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Gastrointestinal disorders Proctitis	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Investigations AST > 8 times upper limit of normal	0.53% 2/379 • Number of events 2 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Investigations Aspartate Aminotransferase Increased	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Investigations Ast Increased	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Investigations Creatinine Serum Increased	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Musculoskeletal and connective tissue disorders CK > 10 times upper limit of normal	1.1% 4/379 • Number of events 4 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	1.1% 4/366 • Number of events 4 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Agitation	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Brain Disorder (Nos)	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Cognitive Disturbance	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Delirium	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Encephalopathy	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Intracerebral Hemorrhage	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Nervous system disorders Stroke	0.53% 2/379 • Number of events 2 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Respiratory, thoracic and mediastinal disorders Aspiration	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Respiratory, thoracic and mediastinal disorders Coughing Blood	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Respiratory, thoracic and mediastinal disorders Embolism Pulmonary	0.53% 2/379 • Number of events 2 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.55% 2/366 • Number of events 2 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Respiratory, thoracic and mediastinal disorders Hypoxemia	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.26% 1/379 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.00% 0/366 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.
Skin and subcutaneous tissue disorders Skin Ulceration	0.00% 0/379 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.	0.27% 1/366 • Number of events 1 • Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first. 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.