Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07368010

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

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

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Palliative Care Death Dying Process Intensive Care Medicine Pathologic Processes Pathological Conditions, Signs and Symptoms Sedation Withdrawal of Life Support

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Protocol for palliative care and life-support withdrawal

Other

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.

Primary outcomes

  1. 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

Secondary outcomes

  1. 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)

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Time from Inclusion to Extubation

    Time frame: From inclusion to date of extubation, assessed up to 28 days

    Time interval between inclusion and extubation

  14. 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

  15. 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.

  16. 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

  17. 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)

  18. 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

  19. 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

  20. 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

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Amélie SEGUIN, MD

CONTACT

[email protected]

02 53 48 22 40 ext. +332

Jean REIGNIER, MD Professor

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Collaborators

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

Registry information

Official study title

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

Acronym: ARREVE-3

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Jan 26, 2026
Registry last updated
Jan 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.