Effect of Intravenous Interferon beta-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome A Randomized Clinical Trial
Por:
Ranieri, VM, Pettila, V, Karvonen, MK, Jalkanen, J, Nightingale, P, Brealey, D, Mancebo, J, Ferrer, R, Mercat, A, Patroniti, N, Quintel, M, Vincent, JL, Okkonen, M, Meziani, F, Bellani, G, MacCallum, N, Creteur, J, Kluge, S, Artigas-Raventos, A, Maksimow, M, Piippo, I, Elima, K, Jalkanen, S, Jalkanen, M, Bellingan, G, INTEREST Study Grp
Publicada:
25 feb 2020
Resumen:
Importance Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) beta-1a may prevent the underlying event of vascular leakage. Objective To determine the efficacy and adverse events of IFN-beta-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 (Pao(2))/fraction of inspired oxygen (Fio(2)) 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 mu g of IFN-beta-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-beta-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-beta-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-beta-1a group and 33 [21.7%] in the placebo group). Conclusions and Relevance Among adults with moderate or severe ARDS, intravenous IFN-beta-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-beta-1a in the management of ARDS.
This randomized trial compares the effects of intravenous interferon beta-1a vs placebo on 28-day mortality and on ventilator-free days in patients with moderate to severe acute respiratory distress syndrome (ARDS).
Filiaciones:
Ranieri, VM:
Alma Mater Studiorum Univ Bologna, Dipartimento Sci Med & Chirurg Anesthesia & Inten, Policlin St Orsola, Bologna, Italy
Pettila, V:
Univ Helsinki, Dept Anesthesiol Intens Care & Pain Med, Div Intens Care, Helsinki, Finland
Helsinki Univ Hosp, Helsinki, Finland
Karvonen, MK:
Faron Pharmaceut Ltd, Turku, Finland
Jalkanen, J:
Faron Pharmaceut Ltd, Turku, Finland
Nightingale, P:
Manchester Univ NHS Fdn Trust, Wythenshawe Hosp, Manchester, Lancs, England
Brealey, D:
Univ Coll London Hosp NHS Fdn Trust, Crit Care, London, England
Univ Coll London Hosp NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Ctr, London, England
UCL, London, England
Mancebo, J:
Hosp Santa Creu & Sant Pau, Dept Intens Care, Barcelona, Spain
Ferrer, R:
VHIR Hosp Univ Vall dHebron UCI, SODIR Res Grp, Dept Intens Care, Barcelona, Spain
Mercat, A:
Univ Angers, CHU Angers, Med Intens Reanimat, Angers, France
Patroniti, N:
Univ Genoa, Dipartimento Sci Diagnost & Integrate, Genoa, Italy
Quintel, M:
Univ Med Gottingen, Anesthesiol & Operat Intens Care Med, Gottingen, Germany
Vincent, JL:
Univ Libre Bruxelles, Erasme Univ Hosp, Dept Intens Care, Brussels, Belgium
Okkonen, M:
Univ Helsinki, Dept Anesthesiol Intens Care & Pain Med, Div Intens Care, Helsinki, Finland
Helsinki Univ Hosp, Helsinki, Finland
Meziani, F:
Univ Strasbourg UNISTRA, Fac Med, Hop Univ Strasbourg, Nouvel Hop Civil,Serv Reanimat, Strasbourg, France
Bellani, G:
Azienda Osped San Gerardo, Milan, Italy
MacCallum, N:
Univ Coll London Hosp NHS Fdn Trust, Crit Care, London, England
Univ Coll London Hosp NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Ctr, London, England
UCL, London, England
Creteur, J:
Univ Libre Bruxelles, Erasme Univ Hosp, Dept Intens Care, Brussels, Belgium
Kluge, S:
Univ Med Ctr Hamburg Eppendorf, Dept Intens Care, Hamburg, Germany
Artigas-Raventos, A:
Autonomous Univ Barcelona, CIBER Enfermedades Resp, Corp Sanitaria Univ Parc Tauli, Sabadell, Spain
Maksimow, M:
Faron Pharmaceut Ltd, Turku, Finland
Piippo, I:
Faron Pharmaceut Ltd, Turku, Finland
Elima, K:
Univ Turku, Med Res Lab, Turku, Finland
Jalkanen, S:
Univ Turku, Med Res Lab, Turku, Finland
Jalkanen, M:
Faron Pharmaceut Ltd, Turku, Finland
Bellingan, G:
Univ Coll London Hosp NHS Fdn Trust, Crit Care, London, England
Univ Coll London Hosp NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Ctr, London, England
UCL, London, England
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