An interventional study of Protocol for palliative care and life-support withdrawal in Palliative Care, Withdrawal of Life Support and Intensive Care Medicine, sponsored by Nantes University Hospital. Not yet recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-26.
Sponsored by Nantes University Hospital · Not applicable, Interventional, and Supportive care
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
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.
456 studies on the registry are indexed under Death; 86 are open to participants now.
This study's planned enrollment of 720 is above the median of 163 across 210 interventional studies indexed under Death.
Browse Death studies →Nantes University Hospital is the lead sponsor of 839 studies on the registry; 195 are open to participants now.
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Exclusion Criteria:
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Relative:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Protocol for life-support withdrawal and palliative care during the withdrawal process
Other: Protocol for palliative care and life-support withdrawal
Withdrawal of life support at the end of life will be performed according to the usual practices of the participating ICUs
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.
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.
Proportion of patients receiving adequate sedation (RASS-5 within one hour before withdrawal of life-sustaining therapies) and withdrawal of mechanical ventilation
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
Evaluation of Sedation
Maximum rate of continuous infusion of each sedative agent administered (within 1 hour before the first withdrawal of life sustaining therapies and death)
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
Evaluation of Sedation
Number of sedative boluses and number of dose escalations of continuous sedation between inclusion and death
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 Medications Other Than Sedatives
Proportion of patients receiving neuromuscular blocking agents, scopolamine, paracetamol (acetaminophen), or 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
Administration of neuromuscular blocking agents
Proportion of patients receiving 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
Administration of scopolamine
Proportion of patients receiving 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
Administration of paracetamol (acetaminophen)
Proportion of patients receiving 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
Administration of Receiving antiemetic agents
Proportion of patients 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
The Semi-Lateral (¾ Lateral) Position
Proportion of patients positioned in the semi-lateral (¾ lateral) position 1 hour before treatment withdrawal and 1 hour before death
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
Life-Sustaining Organ Support Management
Proportion of patients receiving dialysis, vasoactive drug and/or ECMO at inclusion and at death
Time frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Life-Sustaining Organ Support Management
Proportion of patients in whom all life-sustaining therapies are discontinued before death
Time frame: From inclusion to death, assessed up to 28 days
Life-Sustaining Organ Support Management
Proportion of patients in whom all life-sustaining therapies are withdrawn concomitantly
Time frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Life-Sustaining Organ Support Management
Proportion of patients whith immediate extubation
Time frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Time from Inclusion to Extubation
Time interval between inclusion and extubation
Time frame: From inclusion to date of extubation, assessed up to 28 days
Assessment of Sedation
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
Time frame: From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days
Assessment of Pain Management
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.
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
Assessment of Comfort Management
Proportion of patients with airway secretion scores of 3 or 4
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
Assessment of Comfort Management
Proportion of patients with more than one gasp (≥ 2)
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
Assessment of Communication with Relatives
Proportion of relatives who had at least three meetings with ICU caregivers
Time frame: From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Communication with Relatives
Proportion of meetings conducted jointly by a senior physician and a nurse
Time frame: From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Communication with Relatives
Proportion of relatives who had a meeting with a psychologist
Time frame: From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Conflicts
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.
Time frame: From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Conflicts
Level of conflicts between among healthcare professionals, as rated on a 0-10 Likert scale. A higher score indicates a more intense conflict.
Time frame: From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Conflicts
Level of conflicts between among relatives, as rated on a 0-10 Likert scale. A higher score indicates a more intense conflict.
Time frame: From inclusion to date of ICU discharge, assessed up to 28 days
Assessment of Quality of Dying by Relatives
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.
Time frame: From inclusion to 1 month after death of the patient
Anxiety and Depression in Relatives
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.
Time frame: From inclusion to 1, 3, 6, and 12 months after the death of the patient
Post-Traumatic Stress Disorders in Relatives
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.
Time frame: From inclusion to 1, 3, 6, and 12 months after the death of the patient
Prolonged Grief in Relatives
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.
Time frame: From inclusion to 12 months after the death of the patient
Assessment of Quality of Dying by Healthcare Professionals
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.
Time frame: After the death of the patient, assessed up to 28 days
Psychological Impact on Healthcare Professionals
Measure of Moral Distress for Healthcare Professionals (MMD-HP). MMD-HP min = 0, max = 432; Higher scores correlate with increased risk of moral distress.
Time frame: After the death of the patient, assessed up to 28 days
Impact on ICU Organization and Staff
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.
Time frame: Up to 2 years
Impact on ICU Organization and Staff
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.
Time frame: Up to 2 years
Plan to share: Yes
Supporting information: Study protocol
Time frame: 2027
Access criteria: Open access
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