• V Marco Ranieri, Ville Pettilä, Matti K Karvonen, Juho Jalkanen, Peter Nightingale, David Brealey, Jordi Mancebo, Ricard Ferrer, Alain Mercat, Nicolò Patroniti, Michael Quintel, Jean-Louis Vincent, Marjatta Okkonen, Ferhat Meziani, Giacomo Bellani, Niall MacCallum, Jacques Creteur, Stefan Kluge, Antonio Artigas-Raventos, Mikael Maksimow, Ilse Piippo, Kati Elima, Sirpa Jalkanen, Markku Jalkanen, Geoff Bellingan, and INTEREST Study Group.
• Alma Mater Studiorum-Università di Bologna, Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Bologna, Italy.
• JAMA. 2020 Feb 25; 323 (8): 725-733.

ImportanceAcute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.ObjectiveTo determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.Design, Setting, And ParticipantsMulticenter, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (December 2015-December 2017) that included 301 adults with moderate to severe ARDS according to the Berlin definition. The radiological and partial pressure of oxygen, arterial (Pao2)/fraction of inspired oxygen (Fio2) criteria for ARDS had to be met within a 24-hour period, and the administration of the first dose of the study drug had to occur within 48 hours of the diagnosis of ARDS. The last patient visit was on March 6, 2018.InterventionsPatients were randomized to receive an intravenous injection of 10 μg of IFN-β-1a (144 patients) or placebo (152 patients) once daily for 6 days.Main Outcomes And MeasuresThe primary outcome was a score combining death and number of ventilator-free days at day 28 (score ranged from -1 for death to 27 if the patient was off ventilator on the first day). There were 16 secondary outcomes, including 28-day mortality, which were tested hierarchically to control type I error.ResultsAmong 301 patients who were randomized (mean age, 58 years; 103 women [34.2%]), 296 (98.3%) completed the trial and were included in the primary analysis. At 28 days, the median composite score of death and number of ventilator-free days at day 28 was 10 days (interquartile range, -1 to 20) in the IFN-β-1a group and 8.5 days (interquartile range, 0 to 20) in the placebo group (P = .82). There was no significant difference in 28-day mortality between the IFN-β-1a vs placebo groups (26.4% vs 23.0%; difference, 3.4% [95% CI, -8.1% to 14.8%]; P = .53). Seventy-four patients (25.0%) experienced adverse events considered to be related to treatment during the study (41 patients [28.5%] in the IFN-β-1a group and 33 [21.7%] in the placebo group).Conclusions And RelevanceAmong adults with moderate or severe ARDS, intravenous IFN-β-1a administered for 6 days, compared with placebo, resulted in no significant difference in a composite score that included death and number of ventilator-free days over 28 days. These results do not support the use of IFN-β-1a in the management of ARDS.Trial RegistrationClinicalTrials.gov Identifier: NCT02622724.

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