Reducing post-traumatic stress disorder after ICU discharge with the IPREA3 program for discomfort reduction in the ICU: A stepped wedge cluster-randomized controlled study, the PTSD-REA study

Introduction: Critically ill patients in intensive care units (ICUs) are exposed to stressful conditions and experience discomfort from multiple sources, such as the environment or related to care provided in the ICU, depending on the care organizations and patient health status This discomfort may have short-term and long-term consequences for ICU survivors, such as various degrees of anxiety and/or depression or post-traumatic stress disorder (PTSD) (1) which may affect patient's quality of life Reducing discomfort in the ICU has therefore become a major issue IT has already been demonstrated that the implementation of a tailored multicomponent program for discomfort prevention in adult ICUs (named the IPREA3 program): 1) may decrease the selfperceived discomfort in general adult ICU survivors of at the end of their ICU stay, according the results of the IPREA3 study, a cluster-randomized controlled study (2);2) may reduce substantial PTSD symptoms assessed 1 year after ICU discharge, according the results of the AQVAR study, a prospective cohort study inluding patients who were exposed and unexposed to the IPREA3 program (3) These promising results justify the need for a confirmatory study using a randomized design, the PTSD-REA study Methods: The PTSD-REA study is a stepped wedge cluster-randomized interventional study involving 18 French ICUs The cluster level comprises the ICUs, which are the units of randomization Patients hospitalized in the ICUs comprise the individual level The intervention is the implementation of the IPREA3 program, a tailored multicomponent program consisting of assessment of ICUrelated self-perceived discomforts, immediate and monthly feedback to the healthcare team, and site-specific tailored interventions The whole duration of the inclusion period will be 15 months and patients will be followed-up 1 year after ICU discharge During the first month of the inclusion period, no ICU is exposed to the IPREA3 program Every following month, 2 new ICUS of the 18 participating ICUs are randomized to the application of IPREA3 until the end of the inclusion period, leading to 9 steps We considered 3 periods, a control period, an unvariable 5-month learning period for each ICU, and an interventional period during which the IPREA3 program will be applied during more than 5 months until the end of the inclusion period Patients will be included only during the control period and the interventional period For each participating ICU, the durations of the control period and the interventional period range from 1 to 9 months, according the randomization date for crossing over to the IPREA3 program The eligible patients are patients who survived an ICU stay of at least 3 calendar days with an affiliation to a social security scheme The exclusion criteria include death prior to the 1-year follow-up after the index ICU hospitalization, patients under trusteeship, patients with cognitive incapacity, and patients who did not understand French sufficiently to complete the questionnaires exploring psychiatric morbidity All participants provided written informed consent We planned to include 4500 patients during the study, 2250 patients in each group The primary outcome measure is the presence of substantial PTSD symptoms at one year after ICU discharge assessed from the posttraumatic stress-disorder checklist (PCL-5) which is a 20-item selfreport measure for PTSD symptoms according the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) The secondary outcomes are the following : the ICU stay's duration, the number of days with mechanical ventilation, the overall score of discomfort assessed from the IPREA3 questionnaire, the duration of hospital stay after ICU discharge The other secondary outcomes will be asseseed at 1 year after ICU discharge: the number of symptoms in categories A,B,C, D and E, respectively, assessed from the PCL-5, the scores of the sub-scales A and D, respectively, of the questionnaire HAD-S (Hospital and Anxiety Depression Scale), the score obtained from he World Health Organization Quality of Life (WHOQOL-BREF), the number of emergency room visits, hospitalizations, and consulations with a psychologist or psychiatrist during the past year since ICU discharge, return to own home, and occupational status Results: The inclusion period started on November 1, 2020, but was interrupted on March 19, 2020 due to the consequences of the global COVID-19 pandemic on the functionning of French ICUs, when 1252 patients had already been included It is planned to resume the inclusions in the ICUs on September 1, 2020 The provisional date for ending the inclusions without further interruption due to the COVID-19 pandemic is now July 31, 2021 Conclusion: Despite the interruption of the PTSD-REA study due to the COVID-19 pandemic, more than a thousand patients in the control group could be already included The results of the PTSD-REA study are eagerly expected to confirm that applying the IPREA3 program during the ICU stay may reduce substantial PTSD symptoms at 1 year after ICU discharge in general adult ICU survivors