Brief Summary

The goal of this study is to learn if a structured training program for intensive care unit (ICU) staff can reduce health problems after a stay in the ICU in adults.

These health problems are called post-intensive care syndrome (PICS). PICS includes new or worse physical, thinking, or emotional problems after a serious illness. These problems can affect daily activities, independence, memory, mood, and overall quality of life.

The main questions this study aims to answer are:

Does a training program for ICU staff reduce the number of people who develop PICS three months after leaving the hospital? Does the training improve how often ICU teams apply recommended care practices in daily care?

Researchers will compare patients treated before and after the training program to see if the training reduces PICS.

Researchers will also compare ICUs that receive training on the standard ABCDEF care bundle with those that receive training on an expanded care bundle (A-Z), which includes additional practices such as nutrition, sleep, infection prevention, safety measures, and psychological and social support, to see if the expanded approach provides additional benefits.

Before the training program, participating ICUs will collect information about their usual care. ICU staff will then complete the assigned training program. After the training, ICUs will continue to provide usual care, and researchers will record how often the trained care practices are used in daily clinical practice.

Participants are adults who stay in the ICU for at least 48 hours and leave the hospital alive.

Participants will:

Receive usual ICU care Be followed up after hospital discharge at 1, 3, 6, and 12 months Complete tests and questionnaires about physical health, memory, mood, and quality of life

The main result researchers will measure is the number of participants who develop PICS three months after leaving the hospital, focusing on those treated after the training program.

Background and Rationale PROTECT-ICU is a multicenter, implementation-focused study designed to evaluate the impact of a structured educational intervention targeting intensive care unit (ICU) healthcare professionals on adherence to evidence-based care practices and on patient-centered outcomes after critical illness.

Although survival after critical illness has improved, a substantial proportion of ICU survivors develop persistent physical, cognitive, and psychological impairments, commonly referred to as post-intensive care syndrome (PICS). These long-term sequelae are associated with reduced functional recovery, decreased quality of life, and increased healthcare utilization. Despite growing awareness of PICS, effective strategies to prevent or mitigate its development remain insufficiently established.

The ABCDEF bundle provides a structured framework to optimize ICU care processes, integrating key elements related to analgesia, sedation management, ventilatory support, delirium monitoring and prevention, early mobilization, and family engagement. However, adherence remains heterogeneous across ICUs, and its impact on long-term outcomes remains uncertain.

Additional domains of care, including nutritional optimization, sleep quality, infection prevention, minimization of iatrogenic complications, discharge planning, continuity of care, and psychological and social support, may also influence recovery after critical illness. These elements have been incorporated into an expanded A-Z framework developed through multidisciplinary collaboration and expert consensus.

Objectives The primary objective of the PROTECT-ICU study is to evaluate whether implementation of a structured training program for ICU professionals reduces the incidence of post-intensive care syndrome (PICS) at three months after hospital discharge in patients treated after completion of the educational intervention.

Secondary objectives include:

To assess changes in adherence to bundle-based care practices following the training program To evaluate temporal trends in PICS over time To explore whether training on an expanded A-Z framework provides additional benefit compared with training on the standard ABCDEF bundle

Study Design PROTECT-ICU is a multicenter, cluster-randomized, interventional study with a pre-post (before-after) component. Participating ICUs constitute the unit of randomization and implementation.

Following an initial baseline phase, participating ICUs are randomly assigned at the cluster level to receive training on one of two care frameworks:

Training on the standard ABCDEF bundle Training on the expanded A-Z bundle

This cluster-randomized approach is chosen to minimize contamination within centers and to ensure feasibility of implementation in routine clinical practice.

The study includes three sequential phases:

Baseline phase: collection of data on routine clinical practice and baseline adherence to care bundle components Training phase: delivery of a structured educational program to ICU staff according to the assigned training strategy Post-intervention phase: prospective evaluation of adherence to care practices and patient outcomes after completion of the training program

Each ICU contributes data from both baseline and post-intervention periods, enabling within-center comparisons over time as well as between-group comparisons according to the assigned training strategy.

The conceptual framework assumes that the training intervention improves knowledge, team coordination, and consistency of care delivery, leading to increased adherence to evidence-based practices and subsequent improvement in clinically relevant outcomes.

Educational Intervention and Implementation Strategy The intervention consists of a structured, standardized educational training program directed at multidisciplinary ICU teams, including physicians, nurses, and other healthcare professionals involved in direct patient care. The intervention is educational in nature and does not involve direct assignment of treatments at the individual patient level.

The training program is designed to facilitate implementation of evidence-based care practices through a combination of educational and organizational strategies. Training is delivered using standardized materials, including online sessions, presentations, practical checklists, and visual reminders integrated into the clinical environment.

The content of the training is adapted to the assigned intervention group, covering either the ABCDEF bundle alone or the expanded A-Z framework. All materials are centrally developed to ensure consistency across participating centers and are based on current scientific evidence and expert consensus.

After completion of the training program, ICUs continue to provide usual clinical care. The study evaluates the extent to which trained care practices are implemented in routine practice.

Implementation is supported through integration of bundle-related tools into routine workflows. Adherence to care practices is monitored prospectively using standardized data collection tools, allowing assessment of implementation fidelity at both patient and unit levels.

Data Collection and Follow-up Data are collected using a structured electronic case report form that captures ICU-level characteristics, patient baseline variables, daily care processes during ICU admission, and outcomes after hospital discharge.

The data collection system incorporates standardized definitions, validation rules, and consistency checks to ensure data quality and comparability across centers. Data entry is performed locally with centralized oversight and periodic validation procedures.

Participants are followed longitudinally after hospital discharge at predefined time points. Standardized and validated instruments are used to assess physical function, cognitive performance, psychological status, and health-related quality of life.

Outcome Assessment The primary outcome is the incidence of post-intensive care syndrome (PICS) at three months after hospital discharge in patients included after completion of the training intervention.

Secondary analyses will evaluate changes in PICS over time, adherence to care practices, and differences between training strategies.

Analytical Considerations The analysis will account for the hierarchical structure of the data, with patients nested within ICUs and repeated measurements over time. Statistical models will incorporate clustering effects and adjust for relevant covariates.

The primary analysis will estimate the effect of the training intervention on the incidence of PICS at three months, comparing outcomes before and after implementation and between intervention groups.

Multivariable regression and propensity-based approaches will be used to address potential confounding inherent to the cluster-randomized, real-world design, in which allocation is performed at the ICU (cluster) level rather than at the individual patient level. Additional analyses will explore heterogeneity across centers and robustness of findings.

Ethical and Operational Considerations The study is conducted in accordance with applicable ethical and regulatory standards. The intervention targets healthcare professionals and aims to improve delivery of standard care. Clinical management remains under the responsibility of treating teams.

Data confidentiality is ensured through secure systems and compliance with data protection regulations. Study coordination and data quality oversight are managed centrally.

Scientific Relevance PROTECT-ICU addresses the gap between evidence-based recommendations and their consistent implementation in ICU practice. By evaluating whether a structured training intervention improves adherence to multidimensional care strategies and reduces long-term morbidity, the study aims to generate relevant evidence for quality improvement in critical care.

The comparison between training on standard and expanded care frameworks will also provide insight into whether broader, integrative approaches to ICU care offer additional benefit in the prevention of post-ICU complications.

Inclusion Criteria:

1. Adults aged 18 years or older
2. Patients who stay in the intensive care unit (ICU) for at least 48 hours
3. Written informed consent provided by the patient, or by a legal representative or family member if the patient is unable to decide

Exclusion Criteria:

1. Patients with a decision to limit life-sustaining treatments (for example, not starting or stopping treatments such as mechanical ventilation, vasoactive drugs, dialysis, or resuscitation)
2. Patients expected to be discharged from the ICU within the next 24 hours
3. Patients who are unable to attend follow-up visits after hospital discharge (for example, due to relocation, language barriers, transfer to or from another hospital, or inability to attend clinic visits)
4. Patients with a life expectancy of less than 3 months
5. Patients with severe cognitive impairment or severe mental illness before ICU admission that would make assessments difficult
6. Patients with severe brain injury or severe neurological diseases that prevent proper evaluation of physical or cognitive function

Pseudonymized individual participant data (IPD) underlying the results of the primary and secondary analyses will be made available to qualified researchers upon reasonable request. The shared data will include key clinical, functional, cognitive, psychological, and quality of life variables collected during the ICU stay and post-ICU follow-up, as well as data on compliance with ABCDEF packages. The data will be pseudonymized before sharing and will not include direct identifiers. Requests will be reviewed by the PROTECT-ICU Steering Committee to ensure scientific validity, ethical compliance, and compliance with applicable data protection regulations.

Pseudonymized IPD and supporting documents will become available no earlier than 6 months after publication of the primary results and will remain available for at least 5 years thereafter, subject to applicable legal and ethical requirements.

Access to pseudonymized individual medical data will be granted to qualified researchers to conduct scientifically sound, ethically appropriate, and methodologically rigorous analyses related to the objectives of the PROTECT-ICU study. Applications must include a written research proposal describing the study objectives, planned analyses, and statistical methods, as well as confirmation of compliance with applicable data protection and ethics regulations. Prior to data disclosure, a formal data-sharing agreement specifying permitted uses, confidentiality obligations, and publication rights must be signed. Data will be shared via a secure repository or encrypted transfer managed by the coordination center. All requests will be reviewed by the PROTECT-ICU Steering Committee, which will evaluate scientific merit, feasibility, ethical considerations, and compliance with the original consent and regulatory requirements before granting access.

Not applicable. No parties are masked in this study, as the trial is conducted as an open-label, cluster randomized design in which ICU teams and investigators are aware of group allocation.