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Statins for Acutely Injured Lungs From Sepsis (SAILS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Sepsis
Acute Lung Injury
Interventions Drug: Rosuvastatin
Drug: Placebo
Enrollment 745
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rosuvastatin Placebo
Hide 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
Arm/Group Title Rosuvastatin Placebo Total
Hide 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 Number of Baseline Participants 379 366 745
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 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, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 379 participants 366 participants 745 participants
54.2  (17.1) 54.1  (15.6) 54.1  (16.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 participants
Female
195
  51.5%
185
  50.5%
380
  51.0%
Male
184
  48.5%
181
  49.5%
365
  49.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 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%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 participants
American Indian or Alaska Native 1 5 6
Asian 9 7 16
Native Hawaiian or Other Pacific Islander 2 3 5
Black or African American 52 53 105
White 289 301 590
More than one race NA [1]  NA [1]  NA [2] 
Unknown or Not Reported 14 10 24
[1]
not captured
[2]
Total not calculated because data are not available (NA) in one or more arms.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 379 participants 366 participants 745 participants
379 366 745
APACHE III Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 379 participants 366 participants 745 participants
92.1  (28.4) 94.8  (27.9) 93.4  (28.2)
[1]
Measure Description: APACHE III Score: Acute, Physiology, Age, Chronic Health Evaluation III Prognostic System is a measure of hospital mortality risk for critically ill adult patients. Our study used a refined version based on the study by Knause and colleagues (Chest, 1991; 100:1619-36). The score is based on results from addition of 3 groups of variables (physiology, range: 0-252; age: 0-23; and chronic health: 0-24). Overall score range: 0-299; higher number indicates higher risk.
Primary cause of lung injury   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 participants
Aspiration 26 23 49
Multiple Transfusion 3 1 4
Other 7 4 11
Pneumonia 267 260 527
Sepsis 72 73 145
Trauma 2 4 6
[1]
Measure Description: Based on coding of primary vs. secondary by the site; data entry errors account for total count discrepancy.
Baseline Shock   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 participants
173 166 339
[1]
Measure Description: The number of participants who were in shock at the time of randomization. Baseline shock was defined as meeting one of the following conditions: a mean arterial pressure less than 60 mm Hg, receiving a vasopressor (norepinephrine, epinephrine, vasopressin or neosynephrine) at any dose, or receiving dopamine at a dose greater than or equal to 6 mcg/kg/min (or mcg/min) .
PaFiO2:FiO2 ratio less than or equal to 200 mm Hg   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 participants
267 253 520
[1]
Measure Description: The number of participants with a P/F ratio of 200 mm Hg or less at baseline.
Hours from intubation to randomization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 379 participants 366 participants 745 participants
24 hours or less 124 129 253
between 24 and 48 hours 204 192 396
between 48 and 72 hours 41 31 72
more than 72 hours 10 13 23
Unknown 0 1 1
1.Primary Outcome
Title Hospital Mortality to Day 60.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rosuvastatin Placebo
Hide 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.

Overall Number of Participants Analyzed 379 366
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.5
(24.0 to 33.0)
24.9
(20.5 to 29.3)
Hide 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 [Not Specified]
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
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Ventilator Free Days at Study Day 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rosuvastatin Placebo
Hide 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.

Overall Number of Participants Analyzed 379 366
Mean (Standard Deviation)
Unit of Measure: days
15.1  (10.8) 15.1  (11.0)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval 95%
-1.6 to 1.5
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title Organ Failure Free Days at Day 14
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rosuvastatin Placebo
Hide 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.

Overall Number of Participants Analyzed 379 366
Mean (Standard Deviation)
Unit of Measure: days
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
Hide Description [Not Specified]
Time Frame 28 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rosuvastatin Placebo
Hide 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.

Overall Number of Participants Analyzed 379 366
Mean (Standard Deviation)
Unit of Measure: days
14.3  (10.1) 14.4  (10.3)
5.Other Pre-specified Outcome
Title Other Secondary Out-comes
Hide Description Percentage of subjects with Arrhythmia's, Bowel Ischemia, Myocardial Infarction, Ischemic Stroke, and Thromboembolism were measured.
Time Frame 28 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rosuvastatin Placebo
Hide 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.

Overall Number of Participants Analyzed 367 360
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Arrhythmias
9.0
(6.1 to 11.9)
8.4
(5.5 to 11.3)
Bowel Ischemia
1.4
(0.2 to 2.6)
1.9
(0.5 to 3.3)
Myocardial Infarction
0.5
(-0.3 to 1.3)
0.6
(-0.2 to 1.4)
Ischemic Stroke
0.3
(-.03 to 0.9)
0.3
(-0.3 to 0.9)
Thromboembolism
6.3
(3.8 to 8.9)
6.9
(4.4 to 9.5)
6.Other Pre-specified Outcome
Title Changes in Plasma Concentrations of C-reactive Protein (CRP) From Baseline to Day 6 and Day 14
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rosuvastatin Placebo
Hide 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.

Overall Number of Participants Analyzed 229 229
Mean (Standard Deviation)
Unit of Measure: mg/dL
Day 6 -12.9  (27.79) -15.1  (23.26)
Day 14 -19.8  (31.23) -14.8  (26.28)
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
Hide 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 (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Rosuvastatin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/379 (8.97%)      32/366 (8.74%)    
Blood and lymphatic system disorders     
Pancytopenia  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Thrombocytopenia  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Cardiac disorders     
Asystole  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Cardiac Arrest  1  3/379 (0.79%)  3 4/366 (1.09%)  4
Cardiopulmonary Arrest  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Hemorrhage (Nos)  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Thrombosis Venous Arm  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Venous Thrombosis  1  1/379 (0.26%)  1 1/366 (0.27%)  1
Gastrointestinal disorders     
ALT > 8 times upper limit of normal  1  0/379 (0.00%)  0 3/366 (0.82%)  3
Bowel Perforation  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Gastrointestinal Bleeding  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Ischemia Bowel  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Necrosis Bowel  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Obstruction Small Intestine  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Peforation Bowel  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Proctitis  1  1/379 (0.26%)  1 0/366 (0.00%)  0
General disorders     
Hemorrhage Retroperitoneal  1  1/379 (0.26%)  1 1/366 (0.27%)  1
Hyperpyrexia  1  2/379 (0.53%)  2 0/366 (0.00%)  0
Necrosis  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Neuroleptic Malignant Syndrome  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Investigations     
AST > 8 times upper limit of normal  1  2/379 (0.53%)  2 0/366 (0.00%)  0
Aspartate Aminotransferase Increased  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Ast Increased  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Creatinine Serum Increased  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Musculoskeletal and connective tissue disorders     
CK > 10 times upper limit of normal  1  4/379 (1.06%)  4 4/366 (1.09%)  4
Rhabdomyolysis  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Nervous system disorders     
Agitation  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Brain Disorder (Nos)  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Cognitive Disturbance  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Delirium  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Encephalopathy  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Intracerebral Hemorrhage  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Stroke  1  2/379 (0.53%)  2 0/366 (0.00%)  0
Renal and urinary disorders     
Failure Kidney Acute  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pneumothorax  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Aspiration  1  1/379 (0.26%)  1 1/366 (0.27%)  1
Coughing Blood  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Embolism Pulmonary  1  2/379 (0.53%)  2 2/366 (0.55%)  2
Hypoxemia  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Pleural Effusion  1  1/379 (0.26%)  1 0/366 (0.00%)  0
Pneumothorax  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Skin and subcutaneous tissue disorders     
Skin Ulceration  1  0/379 (0.00%)  0 1/366 (0.27%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, COSTART
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rosuvastatin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/379 (0.00%)      0/366 (0.00%)    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David A. Schoenfeld, PhD ARDSNet CCC PI
Organization: ARDS Network
Phone: 617-726-6111
EMail: dschoenfeld@mgh.harvard.edu
Layout table for additonal information
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00979121    
Other Study ID Numbers: 670
N01HR056179 ( Other Grant/Funding Number: NHLBI )
First Submitted: September 16, 2009
First Posted: September 17, 2009
Results First Submitted: August 22, 2014
Results First Posted: October 3, 2014
Last Update Posted: May 16, 2016