Title

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

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    fish oil ...
  • Study Participants

    90
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.
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 Started
Jul 31
2006
Primary Completion
Jan 31
2009
Study Completion
Aug 31
2009
Results Posted
Oct 03
2011
Estimate
Last Update
Oct 03
2011
Estimate

Drug Fish oil (eicosapentaenoic acid and docosahexanoic acid)

Liquid fish oil 7.5cc enterally every 6 hours

1 Experimental

Enteral fish oil

2 Placebo Comparator

Enteral saline

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

Summary

Enteral Fish Oil

Enteral Saline

All Events

Event Type Organ System Event Term Enteral Fish Oil Enteral Saline

Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8

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.

Enteral Fish Oil

43.0
pg/mL (Median)
Inter-Quartile Range: -656.0 to 604.0

Enteral Saline

-241.0
pg/mL (Median)
Inter-Quartile Range: -807.0 to 349.0

Change in BALF Leukotriene B4

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.

Enteral Fish Oil

6.0
pg/mL (Median)
Inter-Quartile Range: -1.0 to 14.0

Enteral Saline

-2.0
pg/mL (Median)
Inter-Quartile Range: -26.0 to 9.0

Change in BALF Interleukin-6

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.

Enteral Fish Oil

-24.0
pg/mL (Median)
Inter-Quartile Range: -340.0 to 51.0

Enteral Saline

-200.0
pg/mL (Median)
Inter-Quartile Range: -692.0 to 0.0

Change in BALF Monocyte Chemotactic Protein-1

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.

Enteral Fish Oil

-150.0
pg/mL (Median)
Inter-Quartile Range: -1812.0 to 93.0

Enteral Saline

-226.0
pg/mL (Median)
Inter-Quartile Range: -752.0 to -38.0

Change in BALF Neutrophil Count

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.

Enteral Fish Oil

-3.0
# of cells/mm^3 (Median)
Inter-Quartile Range: -19.0 to 12.0

Enteral Saline

-10.0
# of cells/mm^3 (Median)
Inter-Quartile Range: -21.0 to 7.0

Static Lung Compliance

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.

Enteral Fish Oil

31.8
L/cm H20 (Mean)
Standard Deviation: 10.1

Enteral Saline

36.3
L/cm H20 (Mean)
Standard Deviation: 20.1

Oxygenation

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.

Enteral Fish Oil

215.4
PaO2/FiO2 (Mean)
Standard Deviation: 92.8

Enteral Saline

174.0
PaO2/FiO2 (Mean)
Standard Deviation: 63.4

Change in Plasma Interleukin-8

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.

Enteral Fish Oil

Enteral Saline

Change in Plasma Surfactant Protein D

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.

Enteral Fish Oil

26.0
pg/mL (Median)
Inter-Quartile Range: -12.0 to 78.0

Enteral Saline

17.0
pg/mL (Median)
Inter-Quartile Range: -36.0 to 68.0

Change in Plasma vonWillebrand Factor

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.

Enteral Fish Oil

116.0
pg/mL (Median)
Inter-Quartile Range: -9.0 to 235.0

Enteral Saline

43.0
pg/mL (Median)
Inter-Quartile Range: -21.0 to 164.0

Change in Plasma Leukotriene B4

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.

Enteral Fish Oil

21.0
pg/mL (Median)
Inter-Quartile Range: 0.0 to 32.0

Enteral Saline

-6.0
pg/mL (Median)
Inter-Quartile Range: -35.0 to 7.0

Change in Plasma Interleukin-6

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.

Enteral Fish Oil

-33.0
pg/mL (Median)
Inter-Quartile Range: -162.0 to -13.0

Enteral Saline

-78.0
pg/mL (Median)
Inter-Quartile Range: -163.0 to -29.0

Change in Plasma Surfactant Protein D

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.

Enteral Fish Oil

25.0
pg/mL (Median)
Inter-Quartile Range: 0.0 to 32.0

Enteral Saline

36.0
pg/mL (Median)
Inter-Quartile Range: 1.0 to 139.0

Change in Plasma vonWillebrand Factor

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.

Enteral Fish Oil

15.0
pg/mL (Median)
Inter-Quartile Range: -103.0 to 158.0

Enteral Saline

68.0
pg/mL (Median)
Inter-Quartile Range: 21.0 to 206.0

Change in Plasma Interleukin-8

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.

Enteral Fish Oil

-1.0
pg/mL (Median)
Inter-Quartile Range: -17.0 to 0.0

Enteral Saline

Change in Plasma Leukotriene B4

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.

Enteral Fish Oil

10.0
pg/mL (Median)
Inter-Quartile Range: 3.0 to 40.0

Enteral Saline

6.0
pg/mL (Median)
Inter-Quartile Range: -22.0 to 14.0

Worst Multiple Organ Dysfunction Score (MODS) During First 28 Days After Study Enrollment

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.

Enteral Fish Oil

8.5
Scores on a scale (Mean)
Standard Deviation: 3.1

Enteral Saline

8.1
Scores on a scale (Mean)
Standard Deviation: 3.3

Ventilator-free Days During First 28 Days After Study Enrollment

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.

Enteral Fish Oil

14.5
Days (Mean)
Standard Deviation: 10.3

Enteral Saline

13.6
Days (Mean)
Standard Deviation: 9.9

ICU-free Days During First 28 Days After Study Enrollment

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.

Enteral Fish Oil

12.2
Days (Mean)
Standard Deviation: 9.8

Enteral Saline

11.2
Days (Mean)
Standard Deviation: 9.7

Hospital Length of Stay

Enteral Fish Oil

23.0
Days (Mean)
Standard Deviation: 18.3

Enteral Saline

27.6
Days (Mean)
Standard Deviation: 20.6

Hospital Mortality

Enteral Fish Oil

9.0
Participants

Enteral Saline

10.0
Participants

60-day Mortality

Enteral Fish Oil

9.0
Participants

Enteral Saline

11.0
Participants

Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8

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.

Enteral Fish Oil

-531.0
pg/mL (Median)
Inter-Quartile Range: -1308.0 to 94.0

Enteral Saline

-298.0
pg/mL (Median)
Inter-Quartile Range: -870.0 to 397.0

Change in BALF Leukotriene B4

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.

Enteral Fish Oil

Enteral Saline

16.0
pg/mL (Median)
Inter-Quartile Range: 0.0 to 50.0

Change in BALF Interleukin-6

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.

Enteral Fish Oil

-52.0
pg/mL (Median)
Inter-Quartile Range: -898.0 to 0.0

Enteral Saline

-198.0
pg/mL (Median)
Inter-Quartile Range: -865.0 to -17.0

Change in BALF Monocyte Chemotactic Protein-1

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.

Enteral Fish Oil

-402.0
pg/mL (Median)
Inter-Quartile Range: -1690.0 to -41.0

Enteral Saline

-670.0
pg/mL (Median)
Inter-Quartile Range: -1057.0 to -151.0

Change in Plasma Interleukin-6

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.

Enteral Fish Oil

-83.0
pg/mL (Median)
Inter-Quartile Range: -174.0 to 14.0

Enteral Saline

-78.0
pg/mL (Median)
Inter-Quartile Range: -163.0 to -29.0

Change in BALF Neutrophil Count

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.

Enteral Fish Oil

-4.0
# of cells/mm^3 (Median)
Inter-Quartile Range: -48.0 to 8.0

Enteral Saline

-10.0
# of cells/mm^3 (Median)
Inter-Quartile Range: -56.0 to 15.0

Total

90
Participants

Age Continuous

49.9
years (Mean)
Standard Deviation: 16.4

Sex: Female, Male

Overall Study

Enteral Fish Oil

Enteral Saline

Drop/Withdrawal Reasons

Enteral Fish Oil

Enteral Saline