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)
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- University of Washington
- Enrollment
- 90
- Locations
- 5
- Primary Endpoint
- Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8
Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
Arms & Interventions
1
Enteral fish oil
Intervention: Fish oil (eicosapentaenoic acid and docosahexanoic acid) (Drug)
2
Enteral saline
Intervention: Fish oil (eicosapentaenoic acid and docosahexanoic acid) (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Hospital Mortality(At end of hospitalization)
- ICU-free Days During First 28 Days After Study Enrollment(28 days)
- Change in Plasma vonWillebrand Factor(Days 1 and 9)
- Change in BALF Leukotriene B4(Days 1 and 9)
- Change in BALF Interleukin-6(Days 1 and 9)
- Change in BALF Monocyte Chemotactic Protein-1(Days 1 and 9)
- Change in BALF Neutrophil Count(Days 1 and 9)
- Static Lung Compliance(Day 5)
- Oxygenation(Day 5)
- Change in Plasma Interleukin-8(Days 1 and 9)
- Change in Plasma Leukotriene B4(Days 1 and 9)
- Change in Plasma Interleukin-6(Days 1 and 9)
- Change in Plasma Surfactant Protein D(Days 1 and 9)
- Worst Multiple Organ Dysfunction Score (MODS) During First 28 Days After Study Enrollment(Throughout hospital stay)
- Ventilator-free Days During First 28 Days After Study Enrollment(28 days)
- 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)
Investigators
Renee Stapleton
Assistant Professor
University of Washington