A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial of Fish Oil (Eicosapentaenoic Acid and Docosahexaenoic Acid) on Lung and Systemic Inflammation in Patients with Acute Lung Injury

Eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), O-3 fatty acids in fish oil, are anti-inflammatory and may improve outcomes in acute lung injury (ALI), but fish oil has only been tested in ALI patients in a commercial enteral formula containing additional nutrients. We conducted a phase II randomized controlled trial to determine if enteral fish oil reduced pulmonary and systemic inflammation in patients with ALI. Mechanically ventilated ALI patients ≥ 18 years were recruited from 4 North American centers. Subjects were randomized within 48 hours of ALI onset to receive enteral fish oil (9.75g EPA and 6.75g DHA per day) or saline placebo for up to 14 days. Bronchoalveolar lavage fluid (BALF) and blood were collected at baseline (day 0), day 4+/-1, and day 8+/-1. The primary endpoint was BALF interleukin(IL)-8 levels. Forty-one participants were randomized to fish oil and 49 to placebo. Enteral fish oil significantly increased serum EPA concentration (p<0.0001). However, there was no significant difference in the change in BALF IL-8 from baseline to day 4 (p=0.37) or day 8 (p=0.55) between the two groups. Changes in LTB 4 from baseline to day 4 were significantly different in both BALF (p=0.04) and plasma (p=0.002), with LTB4 increasing in the fish oil group and decreasing in the placebo group. There were no significant differences in other BALF or plasma biomarkers. At 60 days, 77.5% and 75.6% of the fish oil and placebo group, respectively, were alive (p=0.96 by logrank test). ICU length of stay (11.9+10.6 vs. 17.4+14.8 days, p=0.04) and duration of mechanical ventilation (8.6+/-9.9 vs. 12.9+/-12.2 days, p=0.07) were decreased in the fish oil group, but when these were analyzed as ICU-free and ventilator-free days, no significant differences were found. Severe adverse events were not significantly different. In conclusion, this trial did not demonstrate a clear decrease in markers of pulmonary or systemic inflammation in patients with ALI, and the results do not support the conduct of a larger clinical trial.