Clinical trial NCT00351533: A Phase II Randomized Trial of Fish Oil in Patients With Acute Lung Injury (ALI)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Distress Syndrome, Adult
Acute Lung Injury
Acute Respiratory Distress Syndrome
Keywords: Respiratory distress syndrome, adult
Acute lung injury
Acute respiratory distress syndrome
ARDS, human
Fish oils
Fatty Acids, Omega-3
Docosahexaenoic Acids
Eicosapentaenoic Acid
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: American Thoracic Society
name: Acute Respiratory Distress Syndrome Foundation
name: American Society for Parenteral and Enteral Nutrition
First posted: 2006-07-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8
timeFrame: Days 1 and 5
Secondary outcomes:
measure: Change in BALF Leukotriene B4
timeFrame: Days 1 and 5
measure: Change in BALF Interleukin-6
timeFrame: Days 1 and 5
measure: Change in BALF Monocyte Chemotactic Protein-1
timeFrame: Days 1 and 5
measure: Change in BALF Neutrophil Count
timeFrame: Days 1 and 5
measure: Static Lung Compliance
timeFrame: Day 5
measure: Oxygenation
timeFrame: Day 5
measure: Change in Plasma Interleukin-8
timeFrame: Days 1 and 5
measure: Change in Plasma Leukotriene B4
timeFrame: Days 1 and 5
measure: Change in Plasma Interleukin-6
timeFrame: Days 1 and 5
measure: Change in Plasma Surfactant Protein D
timeFrame: Days 1 and 5
measure: Change in Plasma vonWillebrand Factor
timeFrame: Days 1 and 5
measure: Worst Multiple Organ Dysfunction Score (MODS) During First 28 Days After Study Enrollment
timeFrame: Throughout hospital stay
measure: Ventilator-free Days During First 28 Days After Study Enrollment
timeFrame: 28 days
measure: ICU-free Days During First 28 Days After Study Enrollment
timeFrame: 28 days
measure: Hospital Length of Stay
timeFrame: At end of hospital admission
measure: Hospital Mortality
timeFrame: At end of hospitalization
measure: 60-day Mortality
timeFrame: 60 days from day of enrollment into study
measure: Change in Bronchoalveolar Lavage Fluid (BALF) Interleukin (IL)-8
timeFrame: Days 1 and 9
measure: Change in BALF Leukotriene B4
timeFrame: Days 1 and 9
measure: Change in BALF Interleukin-6
timeFrame: Days 1 and 9
measure: Change in BALF Monocyte Chemotactic Protein-1
timeFrame: Days 1 and 9
measure: Change in BALF Neutrophil Count
timeFrame: Days 1 and 9
measure: Change in Plasma Interleukin-8
timeFrame: Days 1 and 9
measure: Change in Plasma Leukotriene B4
timeFrame: Days 1 and 9
measure: Change in Plasma Interleukin-6
timeFrame: Days 1 and 9
measure: Change in Plasma Surfactant Protein D
timeFrame: Days 1 and 9
measure: Change in Plasma vonWillebrand Factor
timeFrame: Days 1 and 9
Other outcomes:
Locations:
city: Boise
country: United States
facility: St. Alphonsus Medical Center
state: Idaho
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Burlington
country: United States
facility: University of Vermont/Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: University of Vermont
name: Renee D. Stapleton, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: