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

Acute Respiratory Distress Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00351533
• Other study ID #: 28503-A
• Secondary ID: 05-7895-A 03
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2006
• Last updated: August 26, 2011
• Start date: July 2006
• Est. completion date: August 2009

Study information

• Verified date: August 2011
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: August 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Lung Injury
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Fish oil (eicosapentaenoic acid and docosahexanoic acid)
Liquid fish oil 7.5cc enterally every 6 hours

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario
United States	St. Alphonsus Medical Center	Boise	Idaho
United States	University of Vermont/Fletcher Allen Health Care	Burlington	Vermont
United States	Oregon Health Sciences University	Portland	Oregon
United States	Harborview Medical Center	Seattle	Washington

Sponsors (5)

Lead Sponsor	Collaborator
University of Washington	Acute Respiratory Distress Syndrome Foundation, American Society for Parenteral and Enteral Nutrition, American Thoracic Society, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Day 5	No
Secondary	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.	Day 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Days 1 and 5	No
Secondary	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.	Throughout hospital stay	No
Secondary	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.	28 days	No
Secondary	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.	28 days	No
Secondary	Hospital Length of Stay		At end of hospital admission	No
Secondary	Hospital Mortality		At end of hospitalization	No
Secondary	60-day Mortality		60 days from day of enrollment into study	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No
Secondary	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.	Days 1 and 9	No