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Original Investigation
February 17, 2020

Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Author Affiliations
  • 1Alma Mater Studiorum–Università di Bologna, Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant’Orsola, Bologna, Italy
  • 2Division of Intensive Care, Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • 3Faron Pharmaceuticals Ltd, Turku, Finland
  • 4Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom
  • 5Critical Care, University College London Hospitals, NHS Foundation Trust and National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London, London, United Kingdom
  • 6Department of Intensive Care, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
  • 7Department of Intensive Care/SODIR Research Group–VHIR Hospital Universitari Vall d’Hebron UCI, Barcelona, Spain
  • 8Médecine Intensive-Réanimation CHU d’Angers, Université d’Angers, Angers, France
  • 9Dipartimento di scienze diagnostiche e integrate, Università degli studi di Genova, Genova, Italy
  • 10Anesthesiology and Operative Intensive Care Medicine, Universitätsmedizin Göttingen, Göttingen, Germany
  • 11Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
  • 12Université de Strasbourg (UNISTRA), Faculté de Médecine, Hôpitaux universitaires de Strasbourg, Nouvel Hôpital Civil, Service de réanimation, Strasbourg, France
  • 13Azienda Ospedaliera San Gerardo, Milan, Italy
  • 14Department of Intensive Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 15Corporacion Sanitaria Universitaria Parc Tauli CIBER Enfermedades Respiratorias Autonomous University of Barcelona, Sabadell, Spain
  • 16Medicity research Laboratory, University of Turku, Turku, Finland
JAMA. 2020;323(8):725-733. doi:10.1001/jama.2019.22525
Key Points

Question  Does treatment with systemic interferon β-1a provide clinical benefit in adults with moderate or severe acute respiratory distress syndrome?

Findings  In this randomized clinical trial that included 301 patients, intravenous interferon 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 (median, 10.0 vs 8.5 days).

Meaning  These results do not support the use of interferon β-1a in the management of moderate or severe acute respiratory distress syndrome.

Abstract

Importance  Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.

Objective  To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.

Design, Setting, and Participants  Multicenter, 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.

Interventions  Patients 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 Measures  The 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.

Results  Among 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 Relevance  Among 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 Registration  ClinicalTrials.gov Identifier: NCT02622724

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