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

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00351533
First received: July 11, 2006
Last updated: August 26, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Acute Respiratory Distress Syndrome
Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8 [ Time Frame: Days 1 and 5 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in BALF Leukotriene B4 [ Time Frame: Days 1 and 5 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Hospital Mortality [ Time Frame: At end of hospitalization ] [ Designated as safety issue: No ]
  • 60-day Mortality [ Time Frame: 60 days from day of enrollment into study ] [ Designated as safety issue: No ]
  • Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8 [ Time Frame: Days 1 and 9 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 90
Study Start Date: July 2006
Study Completion Date: August 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Enteral fish oil
Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Liquid fish oil 7.5cc enterally every 6 hours
Other Name: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Placebo Comparator: 2
Enteral saline
Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Liquid fish oil 7.5cc enterally every 6 hours
Other Name: Fish oil (eicosapentaenoic acid and docosahexanoic acid)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351533

Locations
United States, Idaho
St. Alphonsus Medical Center
Boise, Idaho, United States, 83706
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Vermont
University of Vermont/Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
United States, Washington
Harborview Medical Center
Seattle, Washington, United States, 98104
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada, M5B1W8
Sponsors and Collaborators
University of Washington
American Thoracic Society
Acute Respiratory Distress Syndrome Foundation
American Society for Parenteral and Enteral Nutrition
Investigators
Principal Investigator: Renee D. Stapleton, MD, MSc University of Vermont
  More Information

No publications provided

Responsible Party: Renee Stapleton, Assistant Professor, University of Washington
ClinicalTrials.gov Identifier: NCT00351533     History of Changes
Other Study ID Numbers: 28503-A, 05-7895-A 03
Study First Received: July 11, 2006
Results First Received: February 16, 2011
Last Updated: August 26, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
Respiratory distress syndrome, adult
Acute lung injury
Acute respiratory distress syndrome
ARDS, human
Fish oils
Fatty Acids, Omega-3
Docosahexaenoic Acids
Eicosapentaenoic Acid

Additional relevant MeSH terms:
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Lung Injury
Respiratory Distress Syndrome, Newborn
Syndrome
Disease
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries

ClinicalTrials.gov processed this record on October 23, 2014