Comparison of the efficacy and safety of FP-1201-lyo (intravenously administered recombinant human interferon beta-1a) and placebo in the treatment of patients with moderate or severe acute respiratory distress syndrome: study protocol for a randomized controlled trial
Por:
Bellingan, G, Brealey, D, Mancebo, J, Mercat, A, Patroniti, N, Pettila, V, Quintel, M, Vincent, JL, Maksimow, M, Jalkanen, M, Piippo, I, Ranieri, VM
Publicada:
13 nov 2017
Resumen:
Background: Acute respiratory distress syndrome (ARDS) results in vascular leakage, inflammation and respiratory failure. There are currently no approved pharmacological treatments for ARDS and standard of care involves treatment of the underlying cause, and supportive care. The vascular leakage may be related to reduced concentrations of local adenosine, which is involved in maintaining endothelial barrier function. Interferon (IFN) beta-1a up-regulates the cell surface ecto-5'-nucleotidase cluster of differentiation 73 (CD73), which increases adenosine levels, and IFN beta-1 may, therefore, be a potential treatment for ARDS. In a phase I/II, open-label study in 37 patients with acute lung injury (ALI)/ARDS, recombinant human IFN beta-1a was well tolerated and mortality rates were significantly lower in treated than in control patients.
Methods/design: In this phase III, double-blind, randomized, parallel-group trial, the efficacy and safety of recombinant human IFN beta-1a (FP-1201-lyo) will be compared with placebo in adult patients with ARDS. Patients will be randomly assigned to receive 10 mu g FP-1201-lyo or placebo administered intravenously once daily for 6 days and will be monitored for 28 days or until discharged from the intensive care unit. Follow-up visits will then take place at days 90, 180 and 360. The primary endpoint is a composite endpoint including any cause of death at 28 days and days free of mechanical ventilation within 28 days among survivors. Secondary endpoints include: all-cause mortality at 28, 90, 180 and 360 days; organ failure-free days; length of hospital stay; pharmacodynamic assessment including measurement of myxovirus resistance protein A concentrations; and measures of quality of life, respiratory and neurological function at 180 and 360 days. The estimated sample size to demonstrate a reduction in the primary outcome between groups from 30% to 15% is 300 patients, and the study will be conducted in 70-80 centers in nine countries across Europe.
Discussion: There are no effective specific treatments for patients with ARDS and mortality rates remain high. The results from this study will provide evidence regarding the efficacy of a potential new therapeutic agent, FP-1201-lyo, in improving the clinical course and outcome for patients with moderate/severe ARDS.
Filiaciones:
Bellingan, G:
Univ Coll London Hosp, Div Crit Care, NHS Fdn Trust, 235 Euston Rd, London NW1 2BU, England
Brealey, D:
Univ Coll London Hosp, Div Crit Care, NHS Fdn Trust, 235 Euston Rd, London NW1 2BU, England
NHS Fdn Trust, Univ Coll London Hosp, NIHR Univ Coll London Hosp Biomed Res Ctr, 235 Euston Rd, London NW1 2BU, England
Mancebo, J:
Hosp Santa Creu & Sant Pau, Dept Intens Care, Carrer St Quinti 89, Barcelona 08026, Spain
Mercat, A:
CHU Angers, Serv Reanimat, 4 Rue Larrey, F-49100 Angers, France
Patroniti, N:
Azienda Osped San Gerardo, Dipartimento Emergenza & Urgenza, Via Giambattista Pergolesi 33, I-20052 Monza, Italy
Pettila, V:
Helsinki Univ Hosp, Dept Intens Care, Haartmaninkatu 4, Helsinki 00290, Finland
Quintel, M:
Univ Med Gottingen, Anesthesiol & Operat Intens Care Med, Robert Koch Str 40, D-37075 Gottingen, Germany
Vincent, JL:
Univ Libre Bruxelles, Erasme Hosp, Dept Intens Care, Route Lennik 808, B-1070 Brussels, Belgium
Maksimow, M:
Faron Pharmaceut Oy, Joukahaisenkatu 6, Turku 20520, Finland
Jalkanen, M:
Faron Pharmaceut Oy, Joukahaisenkatu 6, Turku 20520, Finland
Piippo, I:
Faron Pharmaceut Oy, Joukahaisenkatu 6, Turku 20520, Finland
Ranieri, VM:
Sapienza Univ Rome, Policlin Umberto Hosp 1, Dept Anesthesia & Crit Care Med, Viale Policlin 155, I-00161 Rome, Italy
Gold, Green Published
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