NCT00979121

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
745

participants targeted

Target at P75+ for phase_3 sepsis

Timeline
Completed

Started Jan 2010

Longer than P75 for phase_3 sepsis

Geographic Reach
1 country

40 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 16, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 17, 2009

Completed
4 months until next milestone

Study Start

First participant enrolled

January 1, 2010

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2013

Completed
11 months until next milestone

Results Posted

Study results publicly available

October 3, 2014

Completed
Last Updated

May 16, 2016

Status Verified

August 1, 2014

Enrollment Period

3.8 years

First QC Date

September 16, 2009

Results QC Date

August 22, 2014

Last Update Submit

April 12, 2016

Conditions

Keywords

ALISepsisstatin

Outcome Measures

Primary Outcomes (1)

  • Hospital Mortality to Day 60.

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

    60 days after randomization

Secondary Outcomes (1)

  • Ventilator Free Days at Study Day 28

    time of initiating unassisted breathing to day 28 after study randomization

Other Outcomes (4)

  • Organ Failure Free Days at Day 14

    14 days after randomization

  • ICU Free Days to Day 28

    28 days after randomization

  • Other Secondary Out-comes

    28 days after randomization

  • +1 more other outcomes

Study Arms (2)

Rosuvastatin

ACTIVE COMPARATOR

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: 1. 28 days after randomization or 3 days after ICU discharge (whichever comes first), 2. Discharge from study hospital, 3. Death

Drug: Rosuvastatin

Placebo

PLACEBO COMPARATOR

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

Interventions

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.

Also known as: Crestor
Rosuvastatin

Subjects received placebo by mouth or feeding tube daily for 28 days or until discharged from study hospital.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. Systemic inflammatory response syndrome (SIRS) defined as meeting at least criteria (a) or (b)for a systemic inflammatory response:
  • White blood cell count \>12,000 or \<4,000 or \>10% band forms
  • Body temperature \>38 degrees Celsius (C) (any route) or \<36 degrees C (accepting core temperatures only; indwelling catheter, esophageal, rectal)
  • Heart rate (\> 90 beats/min) or receiving medications that slow heart rate or paced rhythm 2. Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and bacterial meningitis (Appendix A).
  • \. ALI as defined by acute onset of:
  • <!-- -->
  • PaO2 / FiO2 ≤ 300 (intubated). If altitude \> 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760), and
  • Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and
  • Requirement for positive pressure ventilation via an endotracheal tube, and
  • No clinical evidence of left atrial hypertension, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mm Hg. If a patient has a PAOP \> 18 mmHg, then the other criteria must persist for more than 12 hours after the PAOP has declined to ≤ 18 mmHg, and still be within the 48-hour enrollment window.
  • "Acute onset" is defined as follows: the duration of the hypoxemia criterion (#1) and the chest radiograph criterion (#2) must be ≤ 28 days at the time of randomization. Opacities considered "consistent with pulmonary edema" include any patchy or diffuse opacities not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (\> 28 days). The findings of vascular redistribution, indistinct vessels, and indistinct cardiac borders are not considered "consistent with pulmonary edema".
  • All ALI criteria (3a-d above) must occur within the same 24 hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset and no more than 7 days from the initiation of mechanical ventilation. SIRS criteria must occur within the 72 hours before or the 24 hours after ALI onset. Information for determining when these time window criteria were met may come from either the Network hospital or a referring hospital reports.

You may not qualify if:

  • No consent/inability to obtain consent
  • Age less than 18 years
  • More than 7 days since initiation of mechanical ventilation
  • Patient, surrogate, or physician not committed to full support ).
  • Unable to receive or unlikely to absorb enteral study drug
  • Receiving a statin medication within 48 hours of randomization
  • Allergy or intolerance to statins
  • Physician insistence for the use or avoidance of statins during the current hospitalization
  • Creatine Kinase (CK) , alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal
  • Diagnosis of hypothyroidism and not on thyroid replacement therapy
  • Pregnancy or breast feeding
  • Receiving niacin, fenofibrate or cyclosporine, gemfibrozil, atazanavir, lopinavir, ritonavir, daptomycin
  • Severe chronic liver disease
  • Moribund patient not expected to survive 24 hours
  • Chronic respiratory failure defined as PaCO2 \> 60 mm Hg in the outpatient setting
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (40)

University of San Francisco-Fresno Medical Center

Fresno, California, United States

Location

University of California, Davis Medical Center

Sacramento, California, United States

Location

UCSF-Moffitt Hospital

San Francisco, California, United States

Location

University of California, San Francisco (UCSF)-Moffitt Hospital

San Francisco, California, United States

Location

Centura St. Anthony Central Hospital

Denver, Colorado, United States

Location

Denver Health Medical Center

Denver, Colorado, United States

Location

Rose Medical Center

Denver, Colorado, United States

Location

University of Colorado Health Sciences Center

Denver, Colorado, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, United States

Location

Baton Rouge General Hospital-Blue Bonnet

Baton Rouge, Louisiana, United States

Location

Baton Rouge General Hospital-Midcity

Baton Rouge, Louisiana, United States

Location

Earl K. Long Medical Center

Baton Rouge, Louisiana, United States

Location

Our Lady of the Lake Regional Medical Center

Baton Rouge, Louisiana, United States

Location

Medical Center of Louisiana

New Orleans, Louisiana, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, United States

Location

University of Maryland Shock Trauma Center

Baltimore, Maryland, United States

Location

Baystate Medical Center

Springfield, Massachusetts, United States

Location

Rochester Methodist Hospital

Rochester, Minnesota, United States

Location

St. Mary's Hospital, Mayo Clinic

Rochester, Minnesota, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

Durham Regional Medical Center

Durham, North Carolina, United States

Location

Moses Cone Health System

Greensboro, North Carolina, United States

Location

Wesley Long Community Hospital

Greensboro, North Carolina, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

Baylor College of Medicine

Houston, Texas, United States

Location

Intermountain Medical Center

Murray, Utah, United States

Location

McKay-Dee Hospital

Ogden, Utah, United States

Location

Utah Valley Regional Medical Center

Provo, Utah, United States

Location

LDS Hospital

Salt Lake City, Utah, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, United States

Location

Providence Hospital

Everett, Washington, 98201, United States

Location

Harborview Medical Center

Seattle, Washington, United States

Location

University of Washington

Seattle, Washington, United States

Location

Related Publications (4)

  • Yu SY, Ge ZZ, Xiang J, Gao YX, Lu X, Walline JH, Qin MB, Zhu HD, Li Y. Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial. World J Emerg Med. 2022;13(5):367-372. doi: 10.5847/wjem.j.1920-8642.2022.072.

  • Dinglas VD, Hopkins RO, Wozniak AW, Hough CL, Morris PE, Jackson JC, Mendez-Tellez PA, Bienvenu OJ, Ely EW, Colantuoni E, Needham DM. One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial. Thorax. 2016 May;71(5):401-10. doi: 10.1136/thoraxjnl-2015-208017. Epub 2016 Mar 2.

  • Needham DM, Colantuoni E, Dinglas VD, Hough CL, Wozniak AW, Jackson JC, Morris PE, Mendez-Tellez PA, Ely EW, Hopkins RO. Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial. Lancet Respir Med. 2016 Mar;4(3):203-12. doi: 10.1016/S2213-2600(16)00005-9. Epub 2016 Jan 29.

  • National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.

Related Links

MeSH Terms

Conditions

SepsisAcute Lung Injury

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsLung InjuryLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsFluorobenzenesHydrocarbons, FluorinatedHydrocarbons, HalogenatedHydrocarbonsSulfonesSulfur CompoundsPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
David A. Schoenfeld, PhD ARDSNet CCC PI
Organization
ARDS Network

Study Officials

  • Jonathon Truwit, MD

    University of Virginia, Medical Center

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 16, 2009

First Posted

September 17, 2009

Study Start

January 1, 2010

Primary Completion

November 1, 2013

Study Completion

November 1, 2013

Last Updated

May 16, 2016

Results First Posted

October 3, 2014

Record last verified: 2014-08

Locations