TY - JOUR
T1 - RELAx - REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: Protocol for a randomized controlled trial
AU - and for the RELAx Investigators and the PROVE Network Investigators
AU - Algera, Anna Geke
AU - Pisani, Luigi
AU - Bergmans, Dennis C. J.
AU - den Boer, Sylvia
AU - de Borgie, Corianne A. J.
AU - Bosch, Frank H.
AU - Bruin, Karina
AU - Cherpanath, Thomas G.
AU - Determann, Rogier M.
AU - Dondorp, Arjen M.
AU - Dongelmans, Dave A.
AU - Endeman, Henrik
AU - Haringman, Jasper J.
AU - Horn, Janneke
AU - Juffermans, Nicole P.
AU - van Meenen, David M.
AU - van der Meer, Nardo J.
AU - Merkus, Maruschka P.
AU - Moeniralam, Hazra S.
AU - Purmer, Ilse
AU - Tuinman, Pieter Roel
AU - Slabbekoorn, Mathilde
AU - Spronk, Peter E.
AU - Vlaar, Alexander P. J.
AU - Gama de Abreu, Marcelo
AU - Pelosi, Paolo
AU - Serpa Neto, Ary
AU - Schultz, Marcus J.
AU - Paulus, Frederique
PY - 2018
Y1 - 2018
N2 - Background: Evidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population. Methods/Design: The "REstricted versus Liberal positive end-expiratory pressure in patients without ARDS" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h. RELAx will run in 13 ICUs in the Netherlands to enroll 980 patients under invasive ventilation. In all patients, low tidal volumes are used. Patients assigned to ventilation with low PEEP will receive the lowest possible PEEP between 0 and 5 cm H2O, while patients assigned to ventilation with high PEEP will receive PEEP of 8 cm H2O. The primary endpoint is the number of ventilator-free days and being alive at day 28, a composite endpoint for liberation from the ventilator and mortality until day 28, with a noninferiority margin for a difference between groups of 0.5 days. Secondary endpoints are length of stay (LOS), mortality, and occurrence of pulmonary complications, including severe hypoxemia, major atelectasis, need for rescue therapies, pneumonia, pneumothorax, and development of acute respiratory distress syndrome (ARDS). Hemodynamic support and sedation needs will be collected and compared. Discussion: RELAx will be the first sufficiently sized randomized controlled trial in invasively ventilated, critically ill patients with uninjured lungs using a clinically relevant and objective endpoint to determine whether invasive, low-tidal-volume ventilation with low PEEP is noninferior to ventilation with high PEEP.
AB - Background: Evidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population. Methods/Design: The "REstricted versus Liberal positive end-expiratory pressure in patients without ARDS" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h. RELAx will run in 13 ICUs in the Netherlands to enroll 980 patients under invasive ventilation. In all patients, low tidal volumes are used. Patients assigned to ventilation with low PEEP will receive the lowest possible PEEP between 0 and 5 cm H2O, while patients assigned to ventilation with high PEEP will receive PEEP of 8 cm H2O. The primary endpoint is the number of ventilator-free days and being alive at day 28, a composite endpoint for liberation from the ventilator and mortality until day 28, with a noninferiority margin for a difference between groups of 0.5 days. Secondary endpoints are length of stay (LOS), mortality, and occurrence of pulmonary complications, including severe hypoxemia, major atelectasis, need for rescue therapies, pneumonia, pneumothorax, and development of acute respiratory distress syndrome (ARDS). Hemodynamic support and sedation needs will be collected and compared. Discussion: RELAx will be the first sufficiently sized randomized controlled trial in invasively ventilated, critically ill patients with uninjured lungs using a clinically relevant and objective endpoint to determine whether invasive, low-tidal-volume ventilation with low PEEP is noninferior to ventilation with high PEEP.
KW - Data Interpretation, Statistical
KW - Humans
KW - Intensive Care Units
KW - Multicenter Studies as Topic
KW - Positive-Pressure Respiration/adverse effects
KW - Randomized Controlled Trials as Topic
KW - Respiratory Distress Syndrome/therapy
KW - Sample Size
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046693906&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29739430
U2 - https://doi.org/10.1186/s13063-018-2640-5
DO - https://doi.org/10.1186/s13063-018-2640-5
M3 - Article
C2 - 29739430
SN - 1745-6215
VL - 19
SP - 272
JO - Trials
JF - Trials
IS - 1
M1 - 272
ER -