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A Phase II Randomized Trial of Fish Oil in Patients With Acute Lung Injury (ALI)

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: NCT00351533
Recruitment Status : Completed
First Posted : July 13, 2006
Results First Posted : October 3, 2011
Last Update Posted : October 3, 2011
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
American Thoracic Society
Acute Respiratory Distress Syndrome Foundation
American Society for Parenteral and Enteral Nutrition
Information provided by (Responsible Party):
Renee Stapleton, University of Washington

Tracking Information
First Submitted Date  ICMJE July 11, 2006
First Posted Date  ICMJE July 13, 2006
Results First Submitted Date  ICMJE February 16, 2011
Results First Posted Date  ICMJE October 3, 2011
Last Update Posted Date October 3, 2011
Study Start Date  ICMJE July 2006
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2011)
Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8 [ Time Frame: Days 1 and 5 ]
30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
Original Primary Outcome Measures  ICMJE
 (submitted: July 11, 2006)
Bronchoalveolar lavage fluid (BALF) IL-8.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2011)
  • Change in BALF Leukotriene B4 [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Interleukin-6 [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Monocyte Chemotactic Protein-1 [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Neutrophil Count [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent the 2nd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Static Lung Compliance [ Time Frame: Day 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group remained intubated on day 5 and had this outcome available.
  • Oxygenation [ Time Frame: Day 5 ]
    PaO2/FiO2 is the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen. 30 patients in the fish oil group and 36 patients in the enteral saline group remained intubated on day 5 and had this outcome available.
  • Change in Plasma Interleukin-8 [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Leukotriene B4 [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Interleukin-6 [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Surfactant Protein D [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma vonWillebrand Factor [ Time Frame: Days 1 and 5 ]
    30 patients in the fish oil group and 36 patients in the enteral saline group underwent 2nd blood draw on day 5. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Worst Multiple Organ Dysfunction Score (MODS) During First 28 Days After Study Enrollment [ Time Frame: Throughout hospital stay ]
    Full scale name is Multiple Organ Dysfunction Score (MODS), a scale measuring degree of organ dysfunction in critically ill patients. Minimum score is 0 and maximum score is 24, with 0 indicating no organ failure and 24 indicating severe failure of multiple organs.
  • Ventilator-free Days During First 28 Days After Study Enrollment [ Time Frame: 28 days ]
    Ventilator-free days is a common outcome measure in critical care research. A ventilator-free day is a day that a participant is alive and not receiving mechanical ventilation during the first 28 days after s/he enrolled in the study.
  • ICU-free Days During First 28 Days After Study Enrollment [ Time Frame: 28 days ]
    ICU-free days is a common outcome measure in critical care research. An ICU-free day is a day that a participant is alive and not in the intensive care unit (ICU) during the first 28 days after s/he enrolled in the study.
  • Hospital Length of Stay [ Time Frame: At end of hospital admission ]
  • Hospital Mortality [ Time Frame: At end of hospitalization ]
  • 60-day Mortality [ Time Frame: 60 days from day of enrollment into study ]
  • Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Leukotriene B4 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Interleukin-6 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Monocyte Chemotactic Protein-1 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in BALF Neutrophil Count [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent the 3rd bronchoalveolar lavage (BAL). Participants did not undergo BALs after baseline if they were not intubated or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Interleukin-8 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Leukotriene B4 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Interleukin-6 [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma Surfactant Protein D [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
  • Change in Plasma vonWillebrand Factor [ Time Frame: Days 1 and 9 ]
    15 patients in the fish oil group and 27 patients in the enteral saline group underwent 3rd blood draw on day 9. Participants did not undergo blood draws after baseline if they were discharged from the ICU or had expired, but clinical followup data (e.g. mortality) were collected.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2006)
  • BALF leukotriene B4, interleukin-6, interleukin-1β, interleukin-1 receptor antagonist, tumor necrosis factor α, neutrophil count, procollagen peptide III, macrophage inhibitory peptide-1-α, vonWillebrand factor
  • Lung compliance and oxygenation
  • Serum interleukin-8, leukotriene B4, interleukin-6, interleukin-1β
  • Organ failure (quantified by SOFA scores), ventilator-free days during first 28 days, ICU length of stay, hospital length of stay, nosocomial infections, hospital mortality
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Randomized Trial of Fish Oil in Patients With Acute Lung Injury (ALI)
Official Title  ICMJE A Randomized, Double-blind Study of the Effect of Fish Oil (Eicosapentaenoic Acid and Docosahexanoic Acid) on Lung and Systemic Inflammation in Patients With Acute Lung Injury (ALI)
Brief Summary The purpose of this study is to determine whether fish oil (containing omega-3 fatty acids) given enterally is safe and effective in reducing lung and systemic inflammation seen in acute lung injury.
Detailed Description

Acute lung injury (ALI) is common among critically ill patients and is associated with a high case fatality. Only one intervention has been shown to improve survival in a large clinical trial, and new therapies targeting the inflammatory response are needed. Nutrient interventions may provide benefit; specifically there is plausible biologic rationale for administering n-3 fatty acids (n-3 FAs) found in fish oil to patients with ALI, as n-3 FAs decrease formation of eicosanoid inflammatory mediators. However, although promising results have emerged from prior studies, fish oils have only been tested in ALI patients in a commercial enteral formula containing additional nutrients, and the control group received a high-fat enteral formula that may have been proinflammatory. Therefore, no conclusion can be drawn about the independent effect of fish oils. Furthermore, the inclusion of key pharmaconutrients in feeding formulas, instead of delivering them separately as pharmaceuticals, limits exposure to the agent, as intensive care unit (ICU) patients commonly receive less than 60% of prescribed caloric needs. Finally, specialized feeding formulas are very expensive, and it may be substantially cheaper to administer pharmaconutrients separately. We believe it is time to begin to approach nutrient trials in critically ill patients differently -- to move away from including them in feeding formulas and begin delivering them like pharmaceuticals. With appropriate scientific investigation and the use of non-nutrient placebos, this novel and innovative approach is a new paradigm of investigating nutrient delivery to critically ill patients.

This study is a phase II randomized controlled trial to determine the effects of enteral eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), both n-3 FAs found in fish oil, versus placebo on the pulmonary and systemic environments, and on clinical outcomes, in patients with ALI. We will investigate the effect of fish oil administration on several biological markers of injury and inflammation in bronchoalveolar lavage fluid and serum, on pulmonary physiologic outcomes, and on clinical outcomes.

Comparison(s): Mechanically ventilated patients with acute lung injury randomized to receive enteral fish oil versus compared to mechanically ventilated patients with acute lung injury randomized to receive placebo.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Respiratory Distress Syndrome, Adult
  • Acute Lung Injury
  • Acute Respiratory Distress Syndrome
Intervention  ICMJE Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Liquid fish oil 7.5cc enterally every 6 hours
Study Arms  ICMJE
  • Experimental: 1
    Enteral fish oil
    Intervention: Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
  • Placebo Comparator: 2
    Enteral saline
    Intervention: Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 11, 2006)
90
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Requiring positive-pressure mechanical ventilation
  • ALI criteria: PaO2/FiO2 <300, bilateral infiltrates on chest radiograph, no left atrial hypertension
  • Age > 17 years

Exclusion Criteria:

  • Expected ICU length of stay <48 hours
  • Unable to undergo bronchoalveolar lavage at enrollment
  • Unable to obtain enteral access
  • Post-cardiac arrest with suspected significant anoxic brain injury
  • Expected survival < 28 days
  • Pregnant
  • Platelet count < 30,000, active bleeding, or international normalized ratio (INR)>3.0
  • History of ventricular tachycardia or fibrillation
  • Receiving recombinant human activated protein C (rh-APC) for sepsis
  • Acquired immune deficiency syndrome (AIDS) with CD4 count < 200
  • Metastatic cancer
  • History of bone marrow, lung, liver, cardiac, kidney, or pancreas transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00351533
Other Study ID Numbers  ICMJE 28503-A
05-7895-A 03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Renee Stapleton, University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • American Thoracic Society
  • Acute Respiratory Distress Syndrome Foundation
  • American Society for Parenteral and Enteral Nutrition
Investigators  ICMJE
Principal Investigator: Renee D. Stapleton, MD, MSc University of Vermont
PRS Account University of Washington
Verification Date August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP