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Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

RELAx – REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial

Authors: Anna Geke Algera, Luigi Pisani, Dennis C. J. Bergmans, Sylvia den Boer, Corianne A. J. de Borgie, Frank H. Bosch, Karina Bruin, Thomas G. Cherpanath, Rogier M. Determann, Arjen M. Dondorp, Dave A. Dongelmans, Henrik Endeman, Jasper J. Haringman, Janneke Horn, Nicole P. Juffermans, David M. van Meenen, Nardo J. van der Meer, Maruschka P. Merkus, Hazra S. Moeniralam, Ilse Purmer, Pieter Roel Tuinman, Mathilde Slabbekoorn, Peter E. Spronk, Alexander P. J. Vlaar, Marcelo Gama de Abreu, Paolo Pelosi, Ary Serpa Neto, Marcus J. Schultz, Frederique Paulus, for the RELAx Investigators and the PROVE Network Investigators

Published in: Trials | Issue 1/2018

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Abstract

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.

Trial registration

ClinicalTrials.​gov, ID:NCT03167580. Registered on 23 May 2017.
Appendix
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Metadata
Title
RELAx – REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial
Authors
Anna Geke Algera
Luigi Pisani
Dennis C. J. Bergmans
Sylvia den Boer
Corianne A. J. de Borgie
Frank H. Bosch
Karina Bruin
Thomas G. Cherpanath
Rogier M. Determann
Arjen M. Dondorp
Dave A. Dongelmans
Henrik Endeman
Jasper J. Haringman
Janneke Horn
Nicole P. Juffermans
David M. van Meenen
Nardo J. van der Meer
Maruschka P. Merkus
Hazra S. Moeniralam
Ilse Purmer
Pieter Roel Tuinman
Mathilde Slabbekoorn
Peter E. Spronk
Alexander P. J. Vlaar
Marcelo Gama de Abreu
Paolo Pelosi
Ary Serpa Neto
Marcus J. Schultz
Frederique Paulus
for the RELAx Investigators and the PROVE Network Investigators
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2640-5

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