Critical IllnessAWAKE-ICUNCT07710066
Analysis of Weaning of Analgosedation and Kinetics of Emergence in Critically Ill Patients
An observational study of Critical Illness and Mechanical Ventilation, run by Patricia Rodriguez Villamizar.
Trial summary
The goal of this prospective multicenter observational study is to characterize early trajectories of consciousness recovery following the first valid structured awakening trial in mechanically ventilated critically ill adults, a phase that is not captured by current weaning classifications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Mechanical Ventilation, Weaning Invasive Mechanical Ventilation
- What is being tested?
- Structured Awakening Evaluation (SAE)
- Type of treatment
- Surgery or procedure
- How many people
- 500 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2026to 1 Sep 2028
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive adult critically ill patients receiving invasive mechanical ventilation for at least 24 hours who undergo a first valid Structured Awakening Evaluation (SAE) following continuous analgosedation during their ICU stay. The study focuses on patients without acute primary structural brain injury or active neuroprotective sedation, in whom recovery of consciousness, ventilator liberation, and subsequent clinical and patient-centered outcomes can be prospectively characterized.
Who may be able to join
- Adult critically ill patients with acute respiratory failure or requiring invasive mechanical ventilation in the context of critical illness will be consecutively enrolled. Eligible participants must meet all of the following criteria:
- Age ≥18 years.
- Receiving invasive mechanical ventilation for ≥24 hours.
- Prior exposure to continuous analgosedation before undergoing a first valid Structured Awakening Evaluation (SAE) during the ICU stay, as defined by the study's operational criteria.
- Availability of sufficient clinical information to identify the baseline time point (t0) and characterize the first valid Structured Awakening Evaluation according to the study's operational definitions.
- Provision of informed consent for participation in the study.
Who cannot join
- Acute primary structural brain injury in which the level of consciousness is primarily determined by the neurological condition or constitutes a therapeutic target, including but not limited to:
- Moderate or severe traumatic brain injury.
- Subarachnoid hemorrhage.
- Ischemic or hemorrhagic stroke.
- Central nervous system infections.
- Other structural brain injuries requiring therapeutic sedation or goal-directed intensive neurological monitoring.
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- Ongoing therapeutic sedation for neurological indications at the time of the first valid Structured Awakening Evaluation (SAE), including:
- Intracranial hypertension management.
- Status epilepticus.
- Other neuroprotective strategies requiring deep sedation.
- ICU admission following cardiac arrest with return of spontaneous circulation and suspected hypoxic-ischemic brain injury or the need for targeted therapeutic sedation.
- Insufficient clinical information to accurately identify the baseline time point (t0) and characterize the architecture of the first valid Structured Awakening Evaluation.
- Patients receiving extracorporeal life support (ECLS/ECMO), in whom assessment of hemodynamic and respiratory stability before initiation of awakening and liberation from invasive mechanical ventilation is substantially more complex.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Patricia Rodríguez Villamizar, MD, PhD contact
About this study
Official title: AWAKE-ICU: Analysis of Weaning of Analgosedation and Kinetics of Emergence in Critically Ill Patients
The goal of this prospective multicenter observational study is to characterize early trajectories of consciousness recovery following the first valid structured awakening trial in mechanically ventilated critically ill adults, a phase that is not captured by current weaning classifications.
The main questions it aims to answer are:
Read more
- What trajectories of consciousness recovery occur during the first 72 hours after the first valid structured awakening trial?
- Are different early consciousness trajectories associated with clinically relevant outcomes, including successful liberation from mechanical ventilation, delirium, duration of mechanical ventilation, ventilator-free days, mortality, and long-term functional and cognitive outcomes?
Participants will:
- Undergo standardized serial assessments of consciousness during the first 72 hours after the first valid structured awakening trial using the Richmond Agitation-Sedation Scale (RASS) and a standardized motor command assessment.
- Receive daily assessments for delirium and weaning-related outcomes during the ICU stay.
- Be followed for clinical outcomes during hospitalization and for functional and cognitive recovery up to 1 year after ICU admission.
Read the detailed description
Background
Recovery of consciousness following interruption of analgosedation is a critical step during liberation from invasive mechanical ventilation. Although Structured Awakening Evaluations (SAEs) are increasingly incorporated into routine intensive care practice, emergence from analgosedation remains highly heterogeneous and poorly characterized. Existing weaning classifications primarily focus on the duration and outcome of ventilator liberation but do not adequately characterize the transitional phase between analgosedation interruption and recovery of consciousness, despite this being a prerequisite for meaningful participation in the weaning process.
Early emergence from analgosedation may determine a patient's ability to participate in spontaneous breathing trials, achieve successful liberation from mechanical ventilation, develop delirium, and ultimately recover after critical illness. However, the trajectories of emergence during the first days following the first valid SAE and their relationship with clinically relevant outcomes remain largely unknown.
Study Objectives
The primary objective of AWAKE-ICU is to characterize early trajectories of emergence from analgosedation during the first 72 hours following the first valid Structured Awakening Evaluation (SAE) in mechanically ventilated critically ill adults.
Secondary objectives are to evaluate the association between early emergence trajectories and clinically relevant outcomes, including spontaneous breathing trial performance, successful liberation from mechanical ventilation, duration of mechanical ventilation, ventilator-free days, delirium, tracheostomy, ICU and hospital length of stay, mortality, and long-term functional, cognitive, and health-related quality-of-life outcomes up to one year.
Study Design
AWAKE-ICU is a prospective, multicenter, observational cohort study conducted in adult intensive care units. Consecutive eligible patients receiving invasive mechanical ventilation will undergo standardized serial assessments during the first 72 hours following their first valid SAE. Emergence from analgosedation will be evaluated using the Richmond Agitation-Sedation Scale (RASS) together with the ability to follow standardized motor commands, allowing classification into predefined trajectories of consciousness recovery.
Participants will be followed throughout their ICU and hospital stay and subsequently at 90 days and 12 months after ICU admission. By providing the first standardized characterization of emergence from analgosedation after a Structured Awakening Evaluation, AWAKE-ICU aims to improve understanding of this critical transition and to generate evidence supporting more individualized approaches to ventilator liberation and recovery after critical illness.
- Conditions
- Critical Illness, Mechanical Ventilation, Weaning Invasive Mechanical Ventilation, Sedation and Analgesia, Critical Care Medicine, Delirium
- Being tested
- Structured Awakening Evaluation (SAE)
- Keywords
- Emergence from Analgosedation, Structured Awakening Evaluation, Recovery of Consciousness, Mechanical Ventilation, Richmond Agitation-Sedation Scale (RASS), Motor Command Assessment, Consciousness Trajectories, Mechanical Ventilation Weaning, Delayed Awakening
- Medical subject headings
- Critical Illness, Agnosia, Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Structured Awakening Evaluation (SAE)Procedure or surgery
A standardized clinical evaluation performed after interruption or reduction of continuous analgosedation according to the study protocol. The Structured Awakening Evaluation is part of routine clinical care and serves exclusively to define cohort entry and characterize emergence from analgosedation. No experimental intervention is assigned or administered as part of this observational study.
| Study group | Role | What they receive |
|---|---|---|
| Mechanically Ventilated Critically Ill Adults | Adult critically ill patients receiving invasive mechanical ventilation who undergo a first valid Structured Awakening Evaluation (SAE), defined according to the study protocol, following interruption or reduction of continuous analgosedation.
Participants will undergo standardized serial assessments of emergence from analgosedation during the first 72 hours and will be followed throughout hospitalization and up to one year to evaluate clinical, functional and cognitive outcomes. Receives: Procedure: Structured Awakening Evaluation (SAE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Trajectory of consciousness recovery during the first 72 hours following the first valid Structured Awakening Evaluation (SAE)
Distribution (%) of patients classified as State A, B, C or NI according to RASS and standardized command-following assessment at baseline, 6, 12, 24, 48 and 72 hours after the first valid SAE.
Measured: At baseline (initiation of the index Structured Awakening Evaluation) and at 6, 12, 24, 48, and 72 hours after initiation of the index SAE.
Secondary outcomes (8)
Early favorable recovery of consciousness
Percentage of participants achieving State A at any predefined assessment within the first 24 hours following the first valid Structured Awakening Evaluation (SAE). State A is defined as RASS ≥ -2 with correct performance of at least 3 of 4 standardized simple commands.
Measured: From initiation of the index Structured Awakening Evaluation through 24 hours, with assessments at baseline and at 6, 12, and 24 hours.
Time to first extubation attempt
Time in days from initiation of the index Structured Awakening Evaluation to the first removal of the endotracheal tube, excluding removal performed as part of tracheostomy.
Measured: From initiation of the index SAE until the first extubation attempt, tracheostomy, death, ICU discharge, or Day 28 after the index SAE, whichever occurs first, assessed up to 28 days.
Ventilator-free days at Day 28
Number of days alive and free from invasive mechanical ventilation during the first 28 days following the first valid Structured Awakening Evaluation (SAE). Participants who die before Day 28 or remain on invasive mechanical ventilation throughout the entire observation period will be assigned 0 ventilator-free days. In participants who undergo reintubation, only the days following the final extubation that is not followed by another reintubation within the 28-day observation period will be counted as ventilator-free days.
Measured: Day 28 after the first valid SAE.
Delirium-free days at Day 28
Number of days during the first 28 days following the first valid Structured Awakening Evaluation (SAE) on which the participant is alive, remains in the intensive care unit, is evaluable for delirium, and has no delirium on the daily assessment. A participant will be considered evaluable for delirium when at least one valid assessment can be performed during that day with a Richmond Agitation-Sedation Scale (RASS) score ≥ -2. A delirium day will be defined as a day with at least one valid positive assessment using a validated delirium assessment tool, preferably the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Days on which delirium cannot be evaluated will not be counted as either delirium days or delirium-free days. Participants who die before Day 28 will not accumulate delirium-free days after death.
Measured: Day 28 after the first valid SAE.
Intensive care unit length of stay
Number of days from admission to the intensive care unit to ICU discharge or death.
Measured: From ICU admission through ICU discharge or death, assessed up to 12 months after ICU admission.
Hospital length of stay
Number of days from hospital admission to hospital discharge or death.
Measured: From hospital admission through hospital discharge or death, assessed up to 12 months after ICU admission.
Intensive care unit mortality
Percentage of participants who die during the index ICU stay before ICU discharge.
Measured: From ICU admission through ICU discharge or death, assessed up to 12 months after ICU admission.
In-hospital mortality
Percentage of participants who die during the index hospitalization before hospital discharge.
Measured: From hospital admission until hospital discharge, assessed up to 12 months after ICU admission.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Patricia Rodriguez Villamizar
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario 12 de Octubre
- Responsible party
- Sponsor-investigator, Patricia Rodriguez Villamizar, Hospital Universitario 12 de Octubre
- Investigators
- Patricia Rodríguez Villamizar, MD, PhD, Principal investigator, Hospital Universitario 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07710066
- Sponsor's protocol ID
- AWAKE-ICU-01
- Acronym
- AWAKE-ICU
- Status last verified
- Jul 2026
- First submitted
- 1 Jul 2026
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the published results will be made available upon reasonable request to the Principal Investigator after publication of the primary results, subject to approval of a research proposal, data use agreement, and compliance with applicable ethical and data protection regulations.
Publications
Shehabi Y, Bellomo R, Kadiman S, Ti LK, Howe B, Reade MC, Khoo TM, Alias A, Wong YL, Mukhopadhyay A, McArthur C, Seppelt I, Webb SA, Green M, Bailey MJ; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study. Crit Care Med. 2018 Jun;46(6):850-859. doi: 10.1097/CCM.0000000000003071.
PubMed 29498938Szarpak L, Aleksandrowicz D, Karczewska K, Kotfis K. Neurotoxicity of ICU sedatives: we should end the surrogate debate and standardize long-term brain outcomes with a core neuro-outcome set. Intensive Care Med. 2026 May;52(5):1167-1168. doi: 10.1007/s00134-026-08354-0. Epub 2026 Mar 16. No abstract available.
PubMed 41838085Landoni G, Kotani Y, Lomivorotov V. Neurotoxicity of sedative drugs: a matter of concern in adults? Intensive Care Med. 2025 Oct;51(10):1901-1903. doi: 10.1007/s00134-025-08030-9. Epub 2025 Jul 24. No abstract available.
PubMed 40705075Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
PubMed 30113379Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, Herridge M, Ferguson N, Devlin J, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Skrobik Y, Hebert P, Sabri E, Meade M; SLEAP Investigators; Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012 Nov 21;308(19):1985-92. doi: 10.1001/jama.2012.13872.
PubMed 23180503Pham T, Heunks L, Bellani G, Madotto F, Aragao I, Beduneau G, Goligher EC, Grasselli G, Laake JH, Mancebo J, Penuelas O, Piquilloud L, Pesenti A, Wunsch H, van Haren F, Brochard L, Laffey JG; WEAN SAFE Investigators. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study. Lancet Respir Med. 2023 May;11(5):465-476. doi: 10.1016/S2213-2600(22)00449-0. Epub 2023 Jan 21.
PubMed 36693401