Implementation of a digital tool for monitoring and managing the emotional and cognitive sequelae of post-intensive care syndrome: ICURA study protocol for a randomised clinical trial

Abstract

Introduction

Intensive care units (ICUs) can be a particularly challenging environment for patients who are mentally vulnerable. In addition to the physical stress associated with critical illness and its management, there are physiological and psychosocial factors that can negatively impact a patient’s mental health. Approximately half of ICU survivors will experience post-intensive care syndrome, a set of emotional, neuropsychological and physical sequelae that can significantly affect patients’ functionality and quality of life, both in the short and long term. The main objective of this study is to investigate whether the ICU Recovery Answers (ICURA) digital follow-up platform can effectively detect emotional and cognitive problems in critically ill patients and its impact on functionality and health-related quality of life during the first year after ICU discharge.

Methods and analysis

Multicentre longitudinal prospective study involving ICU adult patients, with randomised follow-up comparing a telemedicine monitoring programme versus usual medical care during 1 year after discharge. A total of 360 participants will be recruited during their ICU admission in two hospitals in Spain. Efficacy outcomes will focus on participants’ level of functioning, assessed with the WHO Short Disability Assessment Schedule, and quality of life, measured with the 12-Item Short Form Survey at 1, 6 and 12 months after ICU discharge. Emotional state and cognitive impairment will be evaluated using the Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Treatment-Outcome Post-Traumatic Stress Disorder Scale and the Montreal Cognitive Assessment by telephone at 1, 3, 6, 9 and 12 months after ICU discharge.

Ethics and dissemination

The implementation of this project is expected to have a direct impact on the satisfaction of ICU survivors, improving their well-being, personalised follow-up and quality of life. Results from this study will be disseminated at various scientific conferences, national and international meetings, and will be shared with the general public and other relevant parties. The dissemination of these results will occur through scientific publications, allowing the medical and scientific community to benefit from the study’s findings. Ethics approval from the Ethics Board of Parc Taulí Foundation and Balearic Islands with reference numbers 2022/3031 and IB 5072/22 PI: Protocol version 1 of 18 November 2022.

Trial registration number

NCT06504979.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Multicentre, parallel-group randomised controlled trial design enhances internal validity and reduces selection bias.

• Longitudinal follow-up with repeated assessments over 12 months allows evaluation of temporal changes in outcomes.

• Use of validated and standardised instruments improves reliability and comparability of measurements.

• Exclusion of patients with ICU readmission or major complications may limit representativeness and introduce selection bias.

Introduction

Medical advances have considerably raised survival rates in intensive care units (ICUs), but they have also brought attention to the challenges faced by critically ill patients after hospital discharge. ICU survivors often experience a range of emotional (eg, symptoms of anxiety, depression or post-traumatic stress), cognitive (eg, memory and attention problems)^{1 2} and/or physical difficulties (eg, immobility, pain, etc).3,5 This set of short-term to long-term complications is known as post-intensive care syndrome (PICS)6,8 and has a direct impact on the ability to perform daily activities and on patients’ quality of life⁹: affects their interpersonal relationships and impairs their performance of daily tasks.^{6 9 10} Therefore, ensuring the best possible quality of life and level of functionality for patients after critical illness is crucial.² However, the current limitations of the national health system (NHS) do not allow for the follow-up of emotional, cognitive and physical difficulties after ICU. Integrating digital tools into hybrid protocols, which combine face-to-face and virtual visits, could provide an optimal solution for managing PICS.¹¹

During the COVID-19 pandemic, when face-to-face visits were challenging, we conducted a study that demonstrated telemedicine as a useful and easy-to-apply tool for detecting and managing mental health problems that may appear after hospital discharge in critically ill COVID-19 patients.¹² In this context, our research group developed a telemedicine follow-up application (ICU Recovery Answers (ICURA)) for detecting PICS-related affectations. This platform was well accepted by both COVID-19 patients and clinicians during the pandemic, allowing assessments via digital interface or structured telephone interviews when needed. The platform facilitated participant adherence through automated reminders and flexible assessment modalities.¹²

Hereafter, we present the study protocol for a randomised clinical trial (RCT) using the ICURA platform. The main objective of this study is to investigate whether a telemedicine platform can effectively detect emotional and cognitive problems in critically ill patients, extending beyond those with COVID-19, within the context of routine clinical practice. Secondarily, we aim to assess the impact of this type of follow-up and accompaniment on the functionality and quality of life during the first year of the recovery phase following ICU discharge. The study includes the optimisation of the ICURA telemedicine platform by enhancing data analysis and the visualisation interface, as well as implementing a dashboard for healthcare professionals to collect ICU survivors’ feedback and tailor the most appropriate support based on the patient’s condition. Another key aspect we will address in this study is the identification of factors and individuals vulnerable to developing PICS-related sequelae after their ICU admission which may help to deal with preventive strategies.

The main hypothesis is that the telemedicine platform will perform well, and that patients in the ICURA group will show better functionality and quality of life during the year post-ICU follow-up than those in the control group.

Methods and analysis

The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) reporting guidelines have been used to write this study protocol (see online supplemental material file 2).¹³

Trial design

A two-arm, parallel group, open-label, superiority RCT with a 1:1 allocation ratio has been designed to evaluate the ICURA platform compared with patients receiving standard post-ICU recovery care.

Study setting

Two university hospitals along with their respective research institutes, from two different Autonomous Communities in Spain, will participate in this RCT: Parc Taulí University Hospital with Parc Taulí Research and Innovation Institute (I3PT) in Sabadell, Barcelona (Catalonia) and Son Espases University Hospital with the University of the Balearic Islands-Research Institute of Health Sciences (IDISBA) in Palma, Mallorca (Balearic Islands). Both centres have a total of 63 medical-surgical ICU beds and 28 Intermediate Care Unit beds.

Eligibility criteria

Inclusion criteria: Adult (≥18 years old) critically ill patients admitted to a medical-surgical ICU with an expected ICU stay of ≥ 24 hour and who can give consent on their own or through an authorised representative (eg, a family member).

Exclusion criteria: Neurocritical ICU patients; severe neurological pathology (including dementia or focal brain damage with functional and cognitive impairment) prior to admission to the ICU; severe psychiatric pathology (schizophrenia, bipolar disorder, major depressive disorder) or intellectual disability (IQ<70); Patients who develop secondary complications (infections, stroke, traumatic brain injury or any non-transient acquired brain damage) during ICU discharge, that may compromise the results of the emotional and neuropsychological evaluation during the recovery phase; moderate-severe cognitive impairment (Short-IQCODE>85) that impairs ICU patients’ independent participation in the telemedicine follow-up and accompaniment programme; readmission to ICU within 12 months after discharge from ICU; idiomatic barrier (non-Spanish and/or Catalan speaker); patients with life expectancy <1 year or not subsidiaries of active treatment measures. Written informed consent will be obtained from all participants (or their legal representatives) (see online supplemental material 1).

Intervention

The study is non-interventional during the hospitalisation phase (ICU stay included), poses no additional risk to patients and does not interfere with standard care. After ICU and hospital discharge, all participants will be randomly allocated to the ‘follow-up as usual’ (Control group) or the ‘telemedicine follow-up and accompaniment programme’ (ICURA group), for 1 year during the recovery phase. Figure 1 describes the different stages of the study.

Figure 1. Study diagram. ICU, intensive care unit; PICS, post-intensive care syndrome; QoL, quality of life; SF-12, 12-Item Short Form Survey.

Characteristics of the ICURA telemedicine platform

ICURA is an optimised, stand-alone telemedicine platform for assessing PICS-related sequels in ICU survivors and their families. It has been developed based on the expertise of a team of neuropsychologists, intensivists, nurses and other biomedical researchers experienced from the Translational Research Group in Critically Ill Patient at I3PT. ICURA enables the completion of self-administered questionnaires and facilitates responses to expert-designed questions, allowing for the remote monitoring of emotional, cognitive and physical sequelae in ICU survivors (figure 2). ICURA allows clinicians and researchers to track PICS sequelae by generating a PICS profile based on the responses submitted by survivors of critical illness at different time points following ICU discharge (figure 3). Participants can easily complete the questionnaires using a computer, tablet or smartphone. Data correction and interpretation have been optimised to meet the needs of both patients and professionals, improving follow-up and streamlining the decision-making process within the action protocol. This ensures more accurate and individualised interventions.

Figure 2. Patients ICURA follow-up interface screenshot of each section of ICURA’s interface. ICURA, ICU recovery answers.

Figure 3. Health professional ICURA discharge and follow-up interface screenshots from ICURA participants’ scores during the follow-up phase. ICURA, ICU recovery answers; MOCA, Montreal Cognitive Assessment.

The ICURA telematic monitoring tool was previously validated within the PICS-COVID19 project (ClinicalTrials.gov NCT04422444). In that multicentre cohort study, ICU COVID-19 survivors underwent structured telematic follow-up for 12 months.¹²

Emotional and cognitive status will be assessed at ICU discharge using the Hospital Anxiety and Depression Scale (HADS)^{14 15} and the Montreal Cognitive Assessment.^{16 17} The Functional Ambulatory Category¹⁸ as a functionality measure will also be recorded at ICU discharge. The assistance to physical rehabilitation and the presence of delirium during hospitalisation (medical records) will be recollected.

Experimental group: ICURA group

Patients randomly allocated to the telemedicine follow-up group will receive indications to activate their profile in the ICURA remote monitoring platform to be followed during a year after ICU discharge (see figure 1). The 1-year Telematic Follow-up and Accompaniment Programme includes two main modules:

ICURA assessment: During the follow-up, patients can easily complete the questionnaires from a computer or cell phone (see figure 2). Beyond the telemedicine assessment, to evaluate the presence of cognitive deficits, a neuropsychological screening with the Montreal Cognitive Assessment by Telephone (MOCA-T) will be performed. Post-ICU patients’ scores will be corrected and interpreted in terms of severity (none, low, moderate or severe). ICURA provides a PICS profile for every participant at each point of the screening assessment (1, 3, 6, 9 and 12 months).

Additionally, all ICU participants in the ICURA group will have access to psychoeducational resources available in the webspace (see figure 4). All recommendations of physical exercises and psychological standards have been supervised and approved by the Mental Health and the Physical and Rehabilitation departments of the Parc Taulí University Hospital and are available in the digital resources section of the website (http://www.tauli.cat/institut/projectes-i-xarxes/aplicacions/pics/).¹⁹ This website can only be accessed from Spain.

Figure 4. Digital resources for the ICURA group participants screenshot of the available digital resources: What is Post Intensive Care Syndrome (PICS)? and interesting resources. ICURA, ICU recovery answers.

Control condition: TAU group

Participants assigned to the control group will receive standard clinical process and at 1, 6 and 12 months receive self-administered questionnaires via telephone assessment to evaluate their emotional state and quality of life.

At 12 months, all patients (controls and ICURA) will undergo a face-to-face evaluation to assess their cognitive status using a comprehensive neuropsychological battery of tests. Both groups will fill in the questionnaires without direct feedback on deficits during all the follow-up.

Adherence monitoring and intervention dose

Adherence monitoring: Participant adherence to the follow-up protocol will be assessed throughout the 12-month post-ICU period. At each scheduled assessment point (1, 3, 6, 9 and 12 months), the number of questionnaires completed will be recorded. Additional adherence indicators will include: number of referrals initiated by the study team, number of referral visits attended by participants and frequency of access to digital resources provided through the ICURA platform.

Quantification of the intervention dose: The intervention dose will be quantified based on the frequency and intensity of platform use over the 12-month follow-up. This will include the total number of questionnaires completed by each participant during the follow-up year, number of activated digital resources, including submissions made to access to the digital resources website and the number of visits to that website, number of calls answered for symptom confirmation and number of referrals generated in response to moderate-to-severe symptoms identified through the ICURA platform’s symptom-profiling system.

User experience assessment: At the 12-month in-person visit, a semi-structured interview will be conducted to gather qualitative data on participants’ experiences. This assessment will explore satisfaction with the telematic follow-up as well as with the digital resources, perceived usefulness of the platform and overall acceptability of the remote monitoring approach.

Retention and motivation strategies: To optimise retention and maintain participant engagement, several strategies will be implemented. If a participant does not complete a scheduled questionnaire within 5 days of delivery through the ICURA platform, the study team will initiate a reminder call, with up to three attempts made if contact is not established.

Two communication channels, a dedicated study email address and a WhatsApp messaging line, will be available to facilitate ongoing interaction. These channels will be used to send reminders to complete questionnaires, provide direct links to digital resources, respond to requests for participation reports and deliver basic recommendations such as encouraging follow-up with a primary care physician.

Outcomes

The primary outcomes for evaluating the efficacy of the ICURA platform are the changes in the level of functioning and quality of life of participants between month 1 and month 12 after ICU discharge. This will be evaluated at 12 months after ICU discharge in all participants using the following instruments: (1) the WHO Short Disability Assessment Schedule,^{20 21} calculated using the complex scoring method recommended by the WHO (0–100 range) where higher scores indicate higher levels of disability; and (2) 12-Item Short Form Survey (SF-12)^{22 23} with scores ranging from 0 to 100, where higher scores indicate better physical and mental health functioning.

Secondarily, the emotional state will be assessed with the Generalized Anxiety Disorder-7,^{24 25} Patient Health Questionnaire-9 ^{26 27} and Treatment-Outcome Post-Traumatic Stress Disorder Scale.^{28 29} Cognitive impairment will be assessed with the MOCA-T^{16 17} in both the experimental and control groups (see table 1).

Table 1. Schedule of study procedures after hospital discharge.

	1 month after ICU discharge	3 months after ICU discharge	6 months after ICU discharge	9 months after ICU discharge	12 months after ICU discharge
ICURA group
WHODAS 2.0	x		x		x
SF-12	x		x		x
Barthel questionnaire	x	x	x	x	x
MOCA-T	x	x	x	x	x
GAD-7	x	x	x	x	x
PHQ-9	x	x	x	x	x
TOP-8	x	x	x	x	x
Fatigue questionnaire	x	x	x	x	x
Pain questionnaire	x	x	x	x	x
Feeling of suffocation	x	x	x	x	x
Strength and coordination	x	x	x	x	x
Control group
WHODAS 2.0	x		x		x
SF-12	x		x		x
MOCA-T	x		x		x
PHQ-9	x		x		x
GAD-7	x		x		x
TOP-8	x		x		x

GAD-7, General Anxiety Disorder-7; MOCA-T, Montreal Cognitive Assessment Telephone version; PHQ-9, Patient Health Questionnaire; SF-12, The 12-Ítem Short Form Survey; TOP-8, The eight-item treatment-outcome post-traumatic stress disorder scale; WHODAS, World Health Organization Disability Assessment Schedule 2.0.

Primary and secondary efficacy measures will be assessed telematically in both groups (ICURA and CONTROL) at 1, 6 and 12 months after ICU discharge. All participants (ICURA and CONTROL groups) will be invited to perform a face-to-face comprehensive assessment of the neuropsychological status 1 year after ICU discharge. The face-to-face assessment will allow confirmation of the presence of long-term emotional and cognitive PICS-related disorders by contrasting the data obtained telematically during the follow-up programme and the face-to-face data. In addition, the face-to-face assessment will be used to explore which PICS profiles detected by the screening system in the early recovery phase will predict the chronification of long-term emotional and cognitive disturbances. In the ICURA experimental group, the face-to-face assessment will explore satisfaction with the telematic follow-up as well as with the digital resources, through a semi-structured interview.

Participant timeline

The planned duration of the study is 42 months. Patients will be enrolled consecutively during the first 24 months. The patient’s data regarding their ICU condition will be recorded daily during ICU admission, provided the patient’s consent, within a maximum of 28 days. This is a standardised benchmark in critical care research used to evaluate patient outcomes, mortality and treatment efficacy.^{30 31} This timeframe is chosen because it represents a balance between capturing the acute phase of illness and separating it from long-term, post-acute or chronic mortality factors. The 28-day mark offers a consistent and comparable measure across studies and hospitals and also helps distinguish between acute illness and what is known as chronic critical illness. Both post-ICU outcomes, HADS and MOCA,14,17 will be administered at ICU discharge. The follow-up protocol will be administered according to the data of ICU discharge of the patients allocated to the experimental group, performed at 1, 3, 6, 9 and 12 months after ICU discharge.

Sample size and power calculation

The sample size was calculated based on the results of the PICS-COVID19 study.¹² In this cohort, the SF-12 was used to assess mental health-related quality of life (QoL), and all scores were converted into Z-scores to facilitate interpretation. The median mental health-related QoL scores across five time points (1, 3, 6, 9 and 12 months) ranged from −0.003 to 0.1, with observed values between −1 and 1. Therefore, sample size is based on an expected difference of 0.5 and common SD of 1.3 for the SF-12 mental health z-score change from month 1 at month 12 post-ICU, significance level of 5% and assumed dropout rate of 30%. A sample size of 154 critical illness survivors per group has 80% power to test differences between FAU and ICURA. The study includes two co-primary endpoints, which were prespecified a priori to capture complementary dimensions of post-ICU recovery. These endpoints were interpreted jointly rather than as interchangeable independent primary claims. Under this framework, no formal multiplicity adjustment was applied, as the main statistical implication is reduced power (ie, increased type II error) rather than inflation of type I error. In addition, applying a Bonferroni-type correction would have substantially reduced power in a study with clinically and logistically constrained sample size. Therefore, results should be interpreted in the context of the prespecified co-primary endpoint framework. Assuming a 15% ICU mortality rate, a minimum of 363 patients should be enrolled when admitted to ICU.

Patients’ characteristics will be summarised as medians (25th–75th percentiles) or percentages.

Recruitment

Patients admitted to the ICU will undergo daily assessments throughout their stay. Should they meet the specified eligibility criteria, they, or their designated authorised representative(s), will be approached to obtain consent for participation. In instances where initial consent is secured from an authorised representative (for example, if the patient is comatose, heavily sedated or experiencing delirium), this consent will be formally re-confirmed once the patient regains mental competency. Mental competency is specifically defined by a Richmond Agitation-Sedation Scale (RASS)³² score between −1 and +1, and a Confusion Assessment Method for the ICU (CAM-ICU-7)^{33 34} score of 2 or less. Individuals who decline to participate, those whose authorised representatives decline on their behalf, or patients who, despite prior consent from their representatives, subsequently refuse to participate will all be excluded from the study. No incentives will be offered for participation.

Allocation and blinding

After consent and ICU discharge, patients will be assigned to one of the two study arms using the Research Electronic Data Capture (REDCap) randomisation module. They are randomly allocated to the ‘follow-up as usual’ (FAU group) or the ‘telemedicine follow-up and accompaniment program’ (ICURA group). Since gender and invasive mechanical ventilation (IMV) are relevant factors in the development of emotional and cognitive alterations after ICU,^{35 36} a minimisation method for patient allocation, ensuring adequate representation of both men and women, as well as patients with and without IMV, in both groups.

A blinded research team member, who will not be involved in patient care, intervention, data collection or assessments, will manage this computer-generated procedure. However, assessments will follow standardised procedures and predefined criteria to minimise potential bias. Due to the nature of the intervention, neither other study personnel nor patients will be blinded. Data collection and assessments will also be unblinded. However, an independent statistician will conduct the data analysis in a blinded manner.

ICU data collection and assessments

ICU staff will be aware of the study before starting, and participants will be recruited during their ICU admission. The following data will be collected and assessed from ICU admission to ICU discharge or up to a maximum of 28 days after randomisation by trained study staff or through electronic medical records. Since patients will be admitted to the ICU, no retention problems are expected (see table 2).

Table 2. Schedule of study procedures during ICU and hospital stay.

	Day 0	Day 1	Day …	Day 28/ * ICU discharge	Hospital stay
Enrollment
Eligibility screening	x
Informed consent	x
Random allocation				x
ICU data collection
Sociodemographic characteristics	x
Reason for admission (principal diagnosis)	x
Medical comorbidities (CCI)	x
Severity of illness (APACHE-II)	x
Organ failure (SOFA)	x
Frailty (CFS)	x
Pre-ICU cognitive impairment (SHORT-IQCODE)	x
Pharmacological treatment before ICU	x
Visits allowed during ICU stay (y/n)		x
Mental status (RASS, CAM-ICU)		x	x	x
Ventilatory support (if any)		x	x	x
Pharmacological treatment		x	x	x
Cognitive reserve (CRQ)				x
Cognitive status (MoCA)				x
Functional ambulatory Categories (FAC)				x
Hospital Anxiety and Depression Scale (HADS)				x
Days of invasive MV				x
Days of ICU stay				x
Hospital data collection and assessments
Physiological parameters (wearables)					x
Physical rehabilitation					x
Days of delirium					x
Days of hospital stay					x

APACHE-II, Acute Physiology and Chronic Health disease Classification System II; CAM-ICU, Confusion Assessment Method for the ICU; CCI, Charlson Comorbidity Índex; CFS, Clinical Frailty Scale; CRQ, Cognitive Reserve Questionnaire; FAC, Functional Ambulation Classification; HADS, Hospital Anxiety and Depression Scale; ICU, intensive care unit; MoCA, Montreal cognitive assessment; MV, mechanical ventilation; RASS, Richmond Agitation-Sedation Scale; SHORT-IQCODE, Informant Questionnaire on Cognitive Decline in the Elderly; SOFA, Sequential Organ Failure Assessment.

Sociodemographic and clinical data

Demographic and clinical data before ICU will be obtained from medical records and/or asked to the patient after the consent. Level of consciousness will be assessed at ICU admission with RASS³² and severity with Sequential Organ Failure Assessment.³⁷ Comorbidity (Charlson comorbidity index)³⁸ and frailty (Rockwood Clinical Frailty Scale)³⁹ will be collected at ICU admission. Clinical data (level of consciousness, need for IMV, sedation and opioid treatment and use of benzodiazepines) will be daily recollected during a maximum of 28 days or since ICU discharge. We will daily assess the presence of delirium using the CAM-ICU,^{33 34} and the level of dyspnoea and emotional state in patients with RASS>−1 with a visual analogue scale.

In 40 participants of the ICU cohort from the Parc Taulí University Hospital, we will explore the implementation of wearables (smart bands) during the post-ICU hospitalisation phase to record variables such as heart rate, physical activity and SOp2, etc aiming to generate new information on potential risk factors not yet studied. This exploratory pilot study is designed to evaluate feasibility rather than to determine diagnostic or prognostic relationships. The primary objective is to assess data completeness, usability and temporal patterns of selected physiological variables in a real-world inpatient environment. Accordingly, feasibility outcomes will focus on device adherence and data availability throughout the post-ICU hospitalisation period, including the number of valid recording days per participant, the proportion of expected monitoring time yielding usable data, and the frequency and duration of non-use episodes due to discomfort, intolerance or technical issues.

In addition, a descriptive analysis of continuously recorded physiological parameters (heart rate, heart rate variability indices, body temperature and mobility metrics) will be conducted to characterise their distributions and temporal trajectories from ICU discharge to hospital discharge. For each participant, summary statistics (mean, SD, minimum and maximum) will be calculated over the monitoring period. At the cohort level, results will be presented using measures of central tendency and dispersion, without formal hypothesis testing.

Data management and confidentiality

Care report forms (CRFs) will be kept in locked file cabinets and all personal and clinical data will be stored in separate REDCap databases to guarantee the anonymity and confidentiality of the information collected. These data will be stored for 10 years after the study.

Patients will always be identified by a code, so that clinical data concerning them will never be linked to their personal data.

Statistical methods

To evaluate the effectiveness of the intervention, longitudinal analyses will be conducted using linear mixed-effects models. Random intercepts will be included to account for between-subject heterogeneity at baseline, and random slopes for time will be considered to model individual variability in outcome trajectories. The final random-effects structure will be determined based on model fit criteria and parsimony.

Fixed effects will include time (1, 6, 12 months), intervention group and the interaction between time and intervention group, which constitutes the primary parameter of interest for assessing differential change over time between groups. The models will also adjust for prespecified clinically relevant covariates, including sex, need for IMV and presence of delirium during ICU stay.

The primary analysis will follow the intention-to-treat principle and will include all randomised participants with available outcome data at 1, 6 and/or 12 months after ICU discharge. The primary endpoint is the SF-12 Mental Health Score at 1, 6 and 12 months. Effect estimates will be presented as adjusted mean differences between groups over time with corresponding 95% CIs and two-sided p values.

A secondary per-protocol analysis will be performed, including participants who achieved predefined adherence to the follow-up programme (≥80%) and who completed outcome assessments at 1, 6 and 12 months. This analysis will be considered exploratory and interpreted cautiously due to the potential for selection bias.

The effectiveness of the intervention on PICS-related outcomes (symptoms of anxiety, depression, post-traumatic stress disorder and cognitive function) will be analysed using analogous mixed-effects modelling strategies, with appropriate distributional assumptions depending on the scale and measurement properties of each outcome variable.

Data monitoring

Data monitoring will be performed by the study coordinator, who will oversee all study procedures in accordance with Good Clinical Practice guidelines. Most importantly, she will ensure that written informed consents have been obtained, that (e)CRFs have been created correctly (eg, by including ranges to avoid exceeding minimum and maximum values or by including additional fields to add information to ensure proper recording of data) and that the data are stored securely in locked file cabinets and/or in the REDCap database.

The study coordinator will also evaluate twice a year the data collected for completeness and correctness and provide technical support to the rest of the study staff.

Harms and adverse event reporting

The ICURA study, a two-arm, parallel-group, open-label, superiority randomised controlled trial, has been designed to evaluate the ICURA platform compared with standard post-ICU care. It is important to note that the study is considered non-interventional during the hospitalisation phase (including ICU stay), meaning it poses no additional risks to patients and does not interfere with standard care. Therefore, no reason for interruption or suspension of the trial is foreseen. However, following the European Commission guidelines on the collection, verification and reporting of adverse events arising from clinical trials, in the event of an adverse event that poses a risk to participants or is casually related to the use of the ICURA platform, the principal investigator may interrupt and/or suspend the trial, and the ethics committee and other relevant parties will be informed. For any clinical issues, participants will maintain access to their usual healthcare providers, who will be responsible for medical management. Furthermore, participants will have access to a dedicated telephone line to facilitate direct communication with the research team, which will additionally serve for scheduled follow-up calls.

Auditing and protocol amendment

Staff at each participating centre are tasked with adhering to the established study protocol and are required to report any deviations or requests for changes to the study coordinator, monitor and the principal investigator. All decisions concerning adjustments to study procedures or the protocol itself will be reached through a collective agreement among the collaborating partners. These changes will be communicated to all relevant parties and submitted to the ethics committee for approval before being put into practice, and subsequently updated on ClinicalTrials.gov.

Nevertheless, in urgent situations where the rights, safety and well-being of human participants are at risk, deviations from the study protocol may be implemented without prior ethics committee approval. Any such departure from the protocol must be thoroughly documented within the electronic Case Report Form (eCRF). For quality assurance purposes, the study coordinator, monitor, principal investigator and the ethics committee are granted access to all original source data and study-related records, with the strict obligation to uphold confidentiality.

Ethics and dissemination

Consent or assent

Clinical personnel at each hospital, responsible for identifying and enrolling patients, will secure written informed consent from eligible individuals or their authorised proxies. The consent document comprehensively details the intervention, the scope of data collection and evaluation, and explicitly informs patients of their ongoing right to access, modify, object to or withdraw their data at any point. Participants are also made aware that they retain the option to discontinue their involvement in the study at any time; however, data gathered prior to withdrawal may still be used for the trial’s objectives, unless a specific objection is formally lodged.

Furthermore, patients will be informed that the principal investigator reserves the right to remove them from the study if deemed necessary. Such removal could be prompted by safety concerns, the occurrence of an adverse event linked to the intervention under investigation, or a failure to adhere to established procedures. Should a patient be withdrawn, they will receive a clear explanation for this decision and will continue to receive standard medical care for their condition. Patients removed from the study no longer have access to the ICURA platform for study-related assessments. Nevertheless, they will still be allowed to use the clinical resources available through the link if needed, since research assessments and clinical resources are delivered via different platforms.

Lastly, participants will be informed that their anonymised and confidential data may be shared with external entities, including other research institutions, universities and pertinent regulatory bodies, strictly within the confines of this study’s objectives. It is important to note that this trial does not involve the collection of biological samples.

Dissemination policy and access to data

No study findings will be released until the trial concludes, which is anticipated in March 2027. On completion, the results are slated for submission to scholarly, peer-reviewed journals for publication. Additionally, these findings will be presented at various scientific conferences, encompassing regional, national and international meetings, and will be shared with the general public and other relevant parties. Currently, there are no anticipated limitations or restrictions on the dissemination of these results that will occur through scientific publications, allowing the medical and scientific community to benefit from the study’s findings. The implementation of this project is expected to have a direct impact on the satisfaction of ICU survivors, improving their well-being, personalised follow-up and quality of life. The analysis of risk factors, based on demographic and clinical data, will also contribute to the early detection of long-term mental health difficulties in this population.

Regarding data accessibility, the complete datasets and the statistical code employed in the analysis will be made available to interested parties on reasonable request to the corresponding author(s), but only after the study’s results have been formally published. Similarly, the full study protocol and all informed consent documentation will also be accessible under the same conditions.

Patient and public involvement

Patients or the public were not involved in the design, conduct, reporting or dissemination plans of our research

Discussion

Scientific and social interest in PICS has increased markedly in recent years.⁴⁰ It has emerged as a significant concern in public health, with increasing evidence highlighting its persistent effects on survivors’ quality of life.⁴¹ The detection and follow-up of PICS despite their impact on the functionality and quality of life of the survivors of critical illness is limited and is not included in the care portfolio of the majority of NHS hospitals,⁴² highlighting the critical need for new strategies to address long-term sequelae.⁴³ Considering the increased rates of ICU survival (71%–90%)⁴⁴ and the growing elderly population (20% of the global population will be over age 65 by 2050),^{43 44} an increased use of ICU resources is expected in the coming years.

In this context, telemedicine solutions emerge as a promising alternative to access barriers, offering continuous and personalised follow-up. Recent systematic reviews⁴⁵ have demonstrated the effectiveness of eHealth interventions for PICS. Our study, with the ICURA platform, aims to expand this evidence by evaluating a digital care model that has shown potential in similar contexts^{12 46} and aligns with current purposes to implement digital therapies in the prevention of PICS.⁴⁷ Although the significant impact of the sequelae on the functionality and quality of life of ICU survivors is recognised, the phenotype of patients who will chronify these symptoms is still unknown, especially with respect to the emotional and cognitive sequelae of critical illness. Recent literature has advanced in the construction of predictive models for post-ICU mental disorders,^{48 49} and the development of this project will add knowledge to these issues while generating a direct impact on the generation of new models for the detection and management of PICS. ICURA differs from previous studies on telemedicine-based PICS follow-up by incorporating outcome measurement across all PICS domains, including long-term follow-up and integrating patient-centred approaches, rather than focusing exclusively on biomedical indicators.⁵⁰ Current literature emphasises feasibility and qualitative outcomes, while ICURA expands the knowledge gap including effectiveness and acceptability approaches to provide evidence on clinical impact and implementation strategies.^{45 51 52}

The telemedicine follow-up tool generated in the ICU follow-up and accompaniment project could be able to complement the usual treatment of ICU survivors, allowing continuous follow-up of PICS-related sequelae from hospital discharge until 1 year after. This technological solutions system for the telemedicine detection of PICS could contribute to the improvement of PICS follow-up without increasing the assistance load of clinical professionals and reducing the need for face-to-face evaluations. In addition, early detection of PICS could allow an accurate decision-making process that will lead to the suitable implementation of personalised treatment plans. It also streamlines the detection of candidates for rehabilitation and/or management of PICS, contributing to the optimisation of processes and avoiding the loss of cases within the system.

This study protocol presents important strengths. As a multicentre randomised controlled trial (RCT) confers solid external validity, aligned with current guidelines for effective PICS interventions inside digital health’s paradigm.^{38 41 42 45} Furthermore, the 1-year follow-up is determinant to understand the chronicity of PICS’s emotional and cognitive sequelae, and its impact on mental health.^{39 53} Nevertheless, long-term adherence to the telemedicine intervention is challenging, and the open-label nature of the group assignment is a limitation, which implies that neither participants nor researchers will be blinded and could introduce performance biases, although this risk is mitigated by blinding the statistician. Assessor blinding was not feasible due to operational constraints, which may introduce a potential risk of assessment bias; however, assessments followed standardised procedures and predefined criteria to minimise potential bias. Secondary outcomes will be collected using different administration modes (telephone in the control group and app-based self-report in the ICURA group), which may introduce a mode-of-administration effect (eg, interviewer influence or reporting differences). To minimise this risk, we will use identical validated instruments across groups, apply the same assessment schedule and standardise telephone data collection using predefined scripts and trained staff. In addition, we will address this potential source of bias in the interpretation of findings and will perform sensitivity analyses. The exclusion of patients with ICU readmission within 12 months after discharge and major secondary complications during ICU discharge may limit the inclusion of the most severely ill ICU survivors, potentially introducing selection bias and affecting external validity. However, this approach was intended to reduce clinical heterogeneity and to ensure that outcome assessments reflect the post-ICU recovery trajectory rather than acute deterioration episodes or other unrelated complications, which could substantially confound the interpretation of results.

Finally, and most importantly, the implementation of this project is expected to have a direct impact on the satisfaction of ICU survivors in terms of well-being, personalised follow-up and functional and quality of life improvement. Analysing risk factors, based on demographic and continuous clinical data, could help the early detection of long-term mental health difficulties in ICU survivors.