A Phase II Randomized Trial of Fish Oil in Patients With Acute Lung Injury (ALI)
- Conditions
- Respiratory Distress Syndrome, AdultAcute Lung InjuryAcute Respiratory Distress Syndrome
- Interventions
- Drug: Fish oil (eicosapentaenoic acid and docosahexanoic acid)
- Registration Number
- NCT00351533
- Lead Sponsor
- University of Washington
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- Requiring positive-pressure mechanical ventilation
- ALI criteria: PaO2/FiO2 <300, bilateral infiltrates on chest radiograph, no left atrial hypertension
- Age > 17 years
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Fish oil (eicosapentaenoic acid and docosahexanoic acid) Enteral fish oil 2 Fish oil (eicosapentaenoic acid and docosahexanoic acid) Enteral saline
- Primary Outcome Measures
Name Time Method Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8 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.
- Secondary Outcome Measures
Name Time Method Hospital Mortality At end of hospitalization ICU-free Days During First 28 Days After Study Enrollment 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.
Change in BALF Leukotriene B4 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 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 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 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.
Static Lung Compliance 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 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 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 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 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 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 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.
Worst Multiple Organ Dysfunction Score (MODS) During First 28 Days After Study Enrollment 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 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.
Hospital Length of Stay At end of hospital admission 60-day Mortality 60 days from day of enrollment into study Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8 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.
Trial Locations
- Locations (5)
St. Alphonsus Medical Center
🇺🇸Boise, Idaho, United States
University of Vermont/Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada