End-of-life Care in Mechanically Ventilated Patients: Impact of a Comprehensive Palliative Care Protocol in the Intensive Care Setting (ARREVE-3)

January 20, 2026 updated by: Nantes University Hospital

End-of-life Care in Mechanically Ventilated Patients: Impact of a Comprehensive Training to Palliative Care in the Intensive Care Setting. A Multicenter Cluster Randomised Trial

The ARREVE-3 trial will evaluate whether a structured palliative care protocol can improve end-of-life management for mechanically ventilated ICU patients in whom a decision to withdraw life-sustaining therapies has been made. This cluster-randomized controlled trial compares protocol-based care with usual practice across participating centers. The intervention includes comprehensive guidance on symptom management, sedation, nursing care, withdrawal procedures, and family support, supported by standardized staff training. The primary endpoint is adherence to recommended end-of-life practices, while secondary outcomes assess patient comfort, communication with relatives, and the impact on families and healthcare professionals

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Among ICU patients who die after a decision to withdraw life-sustaining therapies, most are receiving mechanical ventilation (MV). Withdrawal of MV may cause discomfort, and end-of-life practices can have a lasting impact on both families and healthcare professionals. Despite international guidelines and recent legislative changes in France, end-of-life practices in the ICU remain highly variable, indicating substantial opportunities for improvement in patient comfort-focused management.

The ARREVE-3 trial aimes to determine whether a structured palliative care protocol for mechanically ventilated patients undergoing withdrawal of life-sustaining therapies improves the quality of the dying process. Developed in collaboration with palliative care specialists, a psychologist, and a sociologist, the protocol provides standardized guidance on pharmacological and non-pharmacological interventions, including symptom assessment tools, sedation strategies, nursing care, and procedures for withdrawal of life-sustaining treatment. Structured recommendations for support of relatives are also included.

ARREVE-3 is a pragmatic, interventional, cluster-randomized controlled trial, with participating ICUs being unit of randomization to minimize contamination between study arms. ICUs randomized to the intervention arm will apply the palliative care protocol, whereas control ICUs will continue to follow usual care. Physicians and nurses in intervention ICUs will receive standardized training from the coordinating team, complemented by a video-based educational module. Designated local champions within each ICU will support implementation and adherence.to the protocol.

The primary endpoint is adherence to the protocol for end-of-life care. Secondary outcomes include patient comfort, quality of communication with relatives, and the impact of the end-of-life process on relatives and healthcare professionals.

Study Type

Interventional

Enrollment (Estimated)

720

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient:

    • Age ≥ 18 years
    • ICU admission for more than 48 hours
    • Receiving invasive mechanical ventilation
    • A documented decision to withdraw life-sustaining therapies, made through a multidisciplinary collegial process and communicated to the designated surrogate decision-maker, family, or relatives
    • At least one visit from a relative prior to the decision to withdraw life-sustaining therapies
    • Provision of informed consent for study participation, or, if the patient lacks decision-making capacity, consent obtained from a relative or legally authorized representative

  • Relative:

    • Age ≥ 18 years
    • Has received at least one medical update regarding the patient's clinical status from an ICU physician prior to the decision to withdraw life-sustaining therapies
    • Has provided informed consent for study participation

Exclusion Criteria:

  • Patient:

    • Presence of a tracheostomy
    • Brain death or involvement in an organ donation procedure
    • Absence of any visit from a relative
    • Subject to legal guardianship or other legal protection measures
    • Incarcerated patient
    • Participation in another interventional research study focused on end-of-life care
    • Pregnant or breastfeeding woman

  • Relative:

    • Inability to understand or speak French
    • Subject to legal guardianship or other legal protection measures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Palliative care protocol
Protocol for life-support withdrawal and palliative care during the withdrawal process
Other: Protocol for palliative care and life-support withdrawal
In the intervention group, end-of-life care will be provided in accordance with the study protocol, which specifies pharmacological management, nursing care, management of life-sustaining organ support, procedures for the assessment of comfort and pain, and support for relatives. Medical and nursing staff in intervention centers will receive on-site, face-to-face training on the care protocol within each ICU. An instructional video detailing the protocol will also be available.
No Intervention: Usual Care
Withdrawal of life support at the end of life will be performed according to the usual practices of the participating ICUs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess whether, compared with usual care, the implementation of a palliative care protocol for mechanically ventilated patients-combined with dedicated staff training-improves adherence to guidelines.
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving adequate sedation (RASS-5 within one hour before withdrawal of life-sustaining therapies) and withdrawal of mechanical ventilation
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of Sedation
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Maximum rate of continuous infusion of each sedative agent administered (within 1 hour before the first withdrawal of life sustaining therapies and death)
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Evaluation of Sedation
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Number of sedative boluses and number of dose escalations of continuous sedation between inclusion and death
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of Patients Receiving Medications Other Than Sedatives
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving neuromuscular blocking agents, scopolamine, paracetamol (acetaminophen), or antiemetic agents.
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Administration of neuromuscular blocking agents
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving neuromuscular blocking agents
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Administration of scopolamine
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving scopolamine
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Administration of paracetamol (acetaminophen)
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving paracetamol (acetaminophen)
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Administration of Receiving antiemetic agents
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving antiemetic agents
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
The Semi-Lateral (¾ Lateral) Position
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients positioned in the semi-lateral (¾ lateral) position 1 hour before treatment withdrawal and 1 hour before death
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Life-Sustaining Organ Support Management
Time Frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients receiving dialysis, vasoactive drug and/or ECMO at inclusion and at death
From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Life-Sustaining Organ Support Management
Time Frame: From inclusion to death, assessed up to 28 days
Proportion of patients in whom all life-sustaining therapies are discontinued before death
From inclusion to death, assessed up to 28 days
Life-Sustaining Organ Support Management
Time Frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients in whom all life-sustaining therapies are withdrawn concomitantly
From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Life-Sustaining Organ Support Management
Time Frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients whith immediate extubation
From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Time from Inclusion to Extubation
Time Frame: From inclusion to date of extubation, assessed up to 28 days
Time interval between inclusion and extubation
From inclusion to date of extubation, assessed up to 28 days
Assessment of Sedation
Time Frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients with a Richmond Agitation-Sedation Scale (RASS) score of -5 or > -4 (≥ -3) 1 hour before withdrawal of the first life-sustaining therapy (mechanical ventilation, vasopressors, or ECMO) and 1 hour before extubation
From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Assessment of Pain Management
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Higher Behavioral Pain Scale (BPS) score 1 hour before withdrawal of the first life-sustaining therapy (mechanical ventilation, vasopressors, or ECMO); BPS min = 3, max = 12; Higher scores correlate with increased pain intensity.
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Assessment of Comfort Management
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients with airway secretion scores of 3 or 4
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Assessment of Comfort Management
Time Frame: From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Proportion of patients with more than one gasp (≥ 2)
From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days
Assessment of Communication with Relatives
Time Frame: From inclusion to date of ICU discharge, assessed up to 28 days
Proportion of relatives who had at least three meetings with ICU caregivers
From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Communication with Relatives
Time Frame: From inclusion to date of ICU discharge, assessed up to 28 days
Proportion of meetings conducted jointly by a senior physician and a nurse
From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Communication with Relatives
Time Frame: From inclusion to date of ICU discharge, assessed up to 28 days
Proportion of relatives who had a meeting with a psychologist
From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Conflicts
Time Frame: From inclusion to date of ICU discharge, assessed up to 28 days
Level of conflicts between ICU healthcare givers and relatives, as rated on a 0-10 Likert scale. A higher score indicates a more intense conflict.
From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Conflicts
Time Frame: From inclusion to date of ICU discharge, assessed up to 28 days
Level of conflicts between among healthcare professionals, as rated on a 0-10 Likert scale. A higher score indicates a more intense conflict.
From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Conflicts
Time Frame: From inclusion to date of ICU discharge, assessed up to 28 days
Level of conflicts between among relatives, as rated on a 0-10 Likert scale. A higher score indicates a more intense conflict.
From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Quality of Dying by Relatives
Time Frame: From inclusion to 1 month after death of the patient
Quality of Dying and Death questionnaire (QODD-1) assessed 1 month after death, as rated on a 0-10 Likert scale. Higher scores correlate with a more satisfactory level of care.
From inclusion to 1 month after death of the patient
Anxiety and Depression in Relatives
Time Frame: From inclusion to 1, 3, 6, and 12 months after the death of the patient
Hospital Anxiety and Depression Scale (HADS) assessed 1, 3, 6, and 12 months after death. HADS min = 0, max = 42; Higher scores correlate with increased risk of anxiety and depression.
From inclusion to 1, 3, 6, and 12 months after the death of the patient
Post-Traumatic Stress Disorders in Relatives
Time Frame: From inclusion to 1, 3, 6, and 12 months after the death of the patient
Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) assessed 1, 3, 6, and 12 months after death. PCL-5 min = 0, max = 80; Higher scores correlate with increased risk of posttraumatic stress.
From inclusion to 1, 3, 6, and 12 months after the death of the patient
Prolonged Grief in Relatives
Time Frame: From inclusion to 12 months after the death of the patient
Prolonged Grief Disorder scale (PG-13) assessed 12 months after death. PG-13 min = 4, max = 48; Higher scores correlate with increased risk of prolonged grief.
From inclusion to 12 months after the death of the patient
Assessment of Quality of Dying by Healthcare Professionals
Time Frame: After the death of the patient, assessed up to 28 days
Quality of Dying and Death questionnaire (QODD-1), as rated on a 0-10 Likert scale. Higher scores correlate with a more satisfactory level of care.
After the death of the patient, assessed up to 28 days
Psychological Impact on Healthcare Professionals
Time Frame: After the death of the patient, assessed up to 28 days
Measure of Moral Distress for Healthcare Professionals (MMD-HP). MMD-HP min = 0, max = 432; Higher scores correlate with increased risk of moral distress.
After the death of the patient, assessed up to 28 days
Impact on ICU Organization and Staff
Time Frame: Up to 2 years
Perceived Stressors in Intensive Care Units (PS-ICU) assessing burnout at the end of the inclusion period. PS-ICU min = 0, max = 104; Higher scores correlate with increased risk of stress at work.
Up to 2 years
Impact on ICU Organization and Staff
Time Frame: Up to 2 years
Maslach Burnout Inventory (MBI) assessing burnout at the end of the inclusion period. MBI min = 0, max = 132; Higher scores correlate with increased risk of burnout.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Collaborators

University Hospital, Tours
University of Burgundy
Centre Hospitalier Universitaire de Saint Louis APHP

Investigators

  • Principal Investigator: Amélie SEGUIN, MD, Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 10, 2026

Primary Completion (Estimated)

January 10, 2028

Study Completion (Estimated)

January 10, 2029

Study Registration Dates

First Submitted

December 19, 2025

First Submitted That Met QC Criteria

January 20, 2026

First Posted (Actual)

January 26, 2026

Study Record Updates

Last Update Posted (Actual)

January 26, 2026

Last Update Submitted That Met QC Criteria

January 20, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC24_0575

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

2027

IPD Sharing Access Criteria

Open access

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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