"PROTECT-ICU: Impact of an Educational Intervention (PROTECT-ICU)

"PROTECT-ICU: Impact of an Educational Intervention on the Implementation of an Expanded ABCDEF Bundle and Its Effect on Post-Intensive Care Syndrome - A Multicenter Cluster Randomized Clinical Trial."

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.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Post Intensive Care Syndrome (PICS)
• Intervention / Treatment: Behavioral: Standardized Training on the ABCDEF Care Bundle (A-F); Behavioral: Standardized training on the expanded ABCDEF care bundle (A-Z)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: CAROLA GIMENEZ-ESPARZA VICH, MD, MSc; Phone Number: +34639339791; Email: carolagimenezesparzavich@gmail.com

Study Locations

• Spain
  • Alicante
    • Orihuela, Alicante, Spain, 03314
      • Recruiting
      • Vega Baja University Hospital
      • Contact: CAROLA GIMENEZ-ESPARZA VICH, MD,MSc; Phone Number: +34 639339791; Email: carolagimenezesparzavich@gmail.com
      • Contact: Executive Director; Phone Number: +34 678670833; Email: ricardo@semicyuc.org
      • Principal Investigator: CAROLA GIMENEZ-ESPARZA VICH, MD, MSc
  • Murcia
    • Murcia, Murcia, Spain, 30005
      • Not yet recruiting
      • Vega Baja University Hospital
      • Contact: CAROLA GIMENEZ-ESPARZA VICH; Phone Number: 639339791; Email: carolagimenezesparzavich@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Training on Standard ABCDEF Bundle (A-F); Clusters (intensive care units) randomized to this arm will receive a standardized staff training program focused on the standard ABCDEF bundle (A-F). After completion of the training period, adherence to the ABCDEF bundle will be assessed in routine clinical practice using daily data collection tools (CRF) for consecutively admitted eligible ICU participants for up to 21days or until ICU discharge or death, whichever occurs first. Follow-up assessments are scheduled at 1, 3, 6, and 12 months after hospital discharge.	Behavioral: Standardized Training on the ABCDEF Care Bundle (A-F); Description of the intervention - Group 1 (ABCDEF A-F) This intervention consists of a standardized, structured training program for intensive care unit (ICU) staff focused on implementing the classic ABCDEF (A-F) care package. The program includes a month-long online educational course with standardized training materials, written checklists, pocket guides, and visual reminders displayed in the ICU. The training combines theoretical content with practical guidance on the daily clinical application of each component of the package. In addition, face-to-face training sessions are provided to reinforce key concepts and facilitate discussion among ICU staff. At least 75% of the staff in each participating ICU must complete the training, and understanding of the content is assessed through a short post-training questionnaire. Once the training is complete, ICU teams are expected to apply the ABCDEF A-F package in routine daily care and document compliance using standardized daily checklist
Experimental: Training on Expanded ABCDEF Bundle (A-Z); Clusters (intensive care units) randomized to this arm will receive a standardized staff training program focused on an expanded ABCDEF bundle (A-Z), which includes additional care elements beyond A-F. After completion of the training period, adherence to the expanded bundle will be assessed in routine clinical practice using daily data collection tools (CRF) for consecutively admitted eligible ICU participants for up to 21 days or until ICU discharge or death, whichever occurs first. Follow-up assessments are scheduled at 1, 3, 6, and 12 months after hospital discharge.	Behavioral: Standardized training on the expanded ABCDEF care bundle (A-Z); Description of the intervention - Group 2 (ABCDEF A-Z) This intervention consists of a standardized, structured training program for intensive care unit (ICU) staff focused on implementing the expanded ABCDEF (A-Z) care package. The program includes a month-long online educational course with standardized training materials, written checklists, pocket guides, and visual reminders displayed in the ICU. The training combines theoretical content with practical guidance on the daily clinical application of each component of the package, including additional elements beyond the classic package related to nutrition, sleep, infection prevention, safety, discharge planning, rehabilitation, psychological support, and other quality of care measures. In addition, face-to-face training sessions are provided to reinforce key concepts and facilitate discussion among ICU staff. At least 75% of staff members in each participating ICU are required to complete the training, and understanding of the cont

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Post-Intensive Care Syndrome (PICS) at 3 months after hospital discharge following a standardized training program on the standard ABCDEF care bundle	PICS: new or worsened impairment compared with pre-ICU baseline in at least one of the following domains: - Physical: decline in functional status (Barthel Index <100 with ≥10-15 point decrease or change in category) or reduced muscle strength (MRC <48), or impaired mobility (TUG >12 s) or reduced exercise capacity (6-minute walk test <80% predicted, <400 m or decrease ≥30 m) or reduced handgrip strength, (values below age- and sex-adjusted) or nutritional impairment (positive Malnutrition Universal Screening Tool MUST or weight loss >10%) or dyspnea (modified Medical Research Council mMRC ≥2 or worsening ≥1), or impaired pulmonary function (FEV1, FVC or DLCO <80% predicted).; - Cognitive: Informant Questionnaire Cognitive Decline in the Elderly (IQCODE) <3.4 with MoCA <26, or IQCODE 3.4-3.6 with decrease of ≥3 points in Montreal Cognitive Assessment MoCA or change category; - Psychological: Hospital Anxiety and Depression Scale HADS >7 and/or Impact of Event Scale IES-R >22.	3 months after hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to the standard ABCDEF bundle and its individual components after the training intervention	Will be assessed as the proportion of eligible bundle components (A-F) correctly performed and documented per patient-day during ICU stay, using a standardized daily checklist specifically designed for the study, comparing the pre-intervention and post-intervention periods. Each component of the bundle (A: pain assessment and management; B: spontaneous awakening and breathing trials; C: choice and titration of sedation; D: delirium assessment and prevention; E: early mobilization; F: family engagement) will be evaluated individually on a daily basis. For each patient-day, components will be considered eligible based on clinical conditions, and adherence will be calculated as the percentage of correctly implemented components over the total number of eligible components. Overall adherence will be expressed as a continuous percentage at both the patient level and the ICU level. Adherence to each individual component will also be analyzed separately.	From the date of study inclusion until ICU discharge, death, or up to 21 days, whichever occurs first; adherence to the ABCDEF bundle assessed daily during ICU stay.
Variation in global adherence to the ABCDEF bundles across participating ICUs	Global adherence to the ABCDEF bundle will be assessed at the ICU level as the mean percentage of eligible bundle components (A-F) correctly performed and documented per patient-day during ICU stay, using a standardized daily checklist. For each ICU, overall adherence will be calculated as the proportion of completed components over the total number of eligible components across all included patients and study days. Adherence will be expressed as a continuous percentage. This outcome will evaluate variability in adherence between participating ICUs in both the pre-intervention and post-intervention periods. Differences across centers will be described and compared to identify heterogeneity in implementation of the bundle. In addition, the distribution of adherence values across ICUs will be analyzed, including measures of central tendency and dispersion, and variation over time will be explored to assess consistency of implementation.	From the date of study inclusion until ICU discharge, death, or up to 21 days, whichever occurs first; adherence to the ABCDEF bundle assessed daily during ICU stay.
Presence of Post-Intensive Care Syndrome (PICS) at 3 months after hospital discharge following training on the expanded ABCDEF bundle	ICS will be defined as new or worsened impairment compared with pre-ICU baseline in at least one of the following domains: Physical domain: impairment defined by at least one of the following: decline in functional status (Barthel Index <100 with ≥10-15 point decrease or change in category), reduced muscle strength (MRC <48), impaired mobility (Timed Up and Go >12 s), reduced exercise capacity (6-minute walk test <80% predicted, <400 m or decrease ≥30 m), reduced handgrip strength, nutritional impairment (positive MUST or weight loss >10%), dyspnea (mMRC ≥2 or worsening ≥1), or impaired pulmonary function (FEV1, FVC or DLCO <80% predicted).; - Cognitive domain: IQCODE <3.4 with MoCA <26, or IQCODE 3.4-3.6 with a decrease of ≥3 points in MoCA or change in category; - Psychological domain: impairment defined by clinically relevant symptoms (HADS >7 and/or IES-R >22). PICS is considered present if at least one domain is impaired.	1 month, 6 months, and 12 months after hospital discharge
Incidence of delirium during ICU stay after implementation of the training intervention	Delirium will be assessed prospectively during ICU stay using validated and standardized instruments, including the Confusion Assessment Method for the ICU (CAM-ICU) or equivalent tools routinely used at participating centers. Assessments will be performed at least once per shift and only during periods when patients are arousable (e.g., Richmond Agitation-Sedation Scale [RASS] ≥ -3). Delirium will be considered present if at least one positive assessment is recorded during ICU stay. The incidence of delirium will be expressed as the proportion of patients who develop delirium at any time during ICU admission. This outcome will evaluate whether implementation of the structured training intervention on the standard and expanded care bundles is associated with a reduction in the incidence of delirium compared with the pre-intervention period.	From study inclusion until the date of ICU discharge, death, or 21 days after study inclusion, whichever came first.
Adherence to the expanded A-Z bundle and its individual components after the training intervention	Will be assessed as the proportion of eligible components correctly performed and documented per patient-day during ICU stay, using a standardized daily checklist specifically developed for the study. The expanded bundle includes the standard ABCDEF components together with additional evidence-based care elements (G-Z) addressing key domains such as communication, infection prevention, nutrition, respiratory management, sleep, safety, rehabilitation, and discharge planning. Each component will be evaluated individually on a daily basis. Adherence will be calculated as the percentage of correctly implemented components over the total number of eligible components. This outcome will evaluate changes in adherence to the expanded A-Z bundle after implementation of the structured training program, comparing pre-intervention and post-intervention periods. Temporal trends in adherence during ICU stay will also be explored.	During ICU stay, up to 21days or until ICU discharge
Incidence of post-intensive care syndrome (PICS) at 1 month, 6 months, and 12 months after hospital discharge following implementation of the training intervention on the standard and expanded ABCDEF care bundles	Incidence of post-intensive care syndrome (PICS) at 1 month, 6 months, and 12 months after hospital discharge following implementation of the training intervention on the standard and expanded care bundles PICS will be defined as new or worsened impairment in at least one of the following domains: -Physical domain: at least one of the following: decline in functional status (Barthel Index <100 with ≥10-15 point decrease or change in category), reduced muscle strength (MRC <48), impaired mobility (Timed Up and Go >12 s), reduced exercise capacity (6-minute walk test <80% predicted, <400 m or decrease ≥30 m), reduced handgrip strength, nutritional impairment (positive MUST or weight loss >10%), dyspnea (mMRC ≥2 or worsening ≥1), or impaired pulmonary function (FEV1, FVC or DLCO <80% predicted).; - Cognitive domain: IQCODE <3.4 with MoCA <26, or IQCODE 3.4-3.6 with a decrease of ≥3 points in MoCA or change in category; - Psychological domain: (HADS >7 and/or IES-R >22).	1 month, 6 months, and 12 months after hospital discharge
Health-related quality of life (SF-12 Physical and Mental Component Scores)	Health-related quality of life will be assessed using the 12-Item Short Form Survey (SF-12). The Physical Component Summary (PCS) and Mental Component Summary (MCS) scores will be calculated. Impairment will be defined as PCS <50 and/or MCS <50. This outcome will evaluate whether implementation of the training intervention is associated with improvement in SF-12 scores (PCS y MCS) after hospital discharge, comparing participants treated before and after the intervention.	At 1, 3, 6, and 12 months after hospital discharge.
Health-related quality of life (EQ-5D-5L Visual Analogue Scale)	Health-related quality of life will be assessed using the EQ-5D-5L visual analogue scale (VAS). Impairment will be defined as VAS <70. This outcome will evaluate whether implementation of the training intervention is associated with improvement in EQ-5D-5L VAS scores after hospital discharge, comparing participants treated before and after the intervention.	At 1, 3, 6, and 12 months after hospital discharge.
Health-related quality of life (EQ-5D-5L Utility Index)	Health-related quality of life will be assessed using the EQ-5D-5L. Health states derived from the five EQ-5D-5L dimensions will be converted into a single utility index using a validated country-specific value set. The utility index ranges from values below 0 (health states worse than death) to 1 (perfect health). Impairment will be defined as a utility index <0.85. This outcome will evaluate whether implementation of the training intervention is associated with improvement in health-related quality of life after hospital discharge, comparing participants treated before and after the intervention.	At 1, 3, 6, and 12 months after hospital discharge.

Collaborators and Investigators

• Sponsor: Carola Giménez-Esparza Vich
• Investigators: Principal Investigator: CAROLA GIMENEZ-ESPARZA VICH, MD, MSc, Vega Baja University Hospital, Orihuela, Spain

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: critical illness; early mobilization; Sedation management; Post-intensive care syndrome; delirium prevention; Family engagement in intensive care; ABCDEF bundle; Quality of care in intensive care; Staff training in intensive care
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Critical Illness; postintensive care syndrome
• Other Study ID Numbers: MC- 2025-093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No