Analysis of Weaning of Analgosedation and Kinetics of Emergence in Critically Ill Patients

NCT07710066 | Not Yet Recruiting

• 1 other identifier: AWAKE-ICU-01
• Study Type: observational
• Target: 500
• Locations: 0 countries
• Sites: N/A

Brief 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. The main questions it aims to answer are:

1. 1.What trajectories of consciousness recovery occur during the first 72 hours after the first valid structured awakening trial?
2. 2.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?
3. 3.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.
4. 4.Receive daily assessments for delirium and weaning-related outcomes during the ICU stay.
5. 5.Be followed for clinical outcomes during hospitalization and for functional and cognitive recovery up to 1 year after ICU admission.

Conditions

Critical Illness; Mechanical Ventilation; Delirium; Weaning Invasive Mechanical Ventilation; Sedation and Analgesia; Critical Care Medicine

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  Day 28 after the first valid SAE.

• Delirium-free days at Day 28

  Day 28 after the first valid SAE.

• Intensive care unit length of stay

  From ICU admission through ICU discharge or death, assessed up to 12 months after ICU admission.

Other Outcomes (14)

• Tolerance of the index Structured Awakening Evaluation

  Assessed during the index Structured Awakening Evaluation, within 2 hours of SAE initiation.

• Intercurrent clinical factors during the first 72 hours after the index Structured Awakening Evaluation

  From initiation of the index Structured Awakening Evaluation through 72 hours after initiation of the index SAE.

• Diagnostic testing prompted by delayed awakening

  From completion of the index Structured Awakening Evaluation through ICU discharge, death, or 28 days after the index SAE, whichever occurs first.

Study Arms (1)

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.

Procedure: Structured Awakening Evaluation (SAE)

Interventions

Structured Awakening Evaluation (SAE) PROCEDURE

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.

Mechanically Ventilated Critically Ill Adults

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Patricia Rodriguez Villamizar: lead
• Fundación para la Investigación Biomédica Hospital Universitario 12 de Octubre: collaborator

Related Publications (6)

• 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.

  PMID: 29498938 BACKGROUND

• Szarpak 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.

  PMID: 41838085 BACKGROUND

• Landoni 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.

  PMID: 40705075 BACKGROUND

• Devlin 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.

  PMID: 30113379 BACKGROUND

• Mehta 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.

  PMID: 23180503 BACKGROUND

• Pham 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.

  PMID: 36693401 BACKGROUND

MeSH Terms

Conditions

Critical Illness; Agnosia; Delirium

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Confusion; Neurocognitive Disorders; Mental Disorders

Study Officials

• Patricia Rodríguez Villamizar, MD, PhD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patricia Rodríguez Villamizar, MD, PhD

CONTACT

+34 699 220 215; patricia.rodriguez.villamizar@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Intensivist and Clinical Researcher

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 17, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 6 months after publication of the primary manuscript up to 5 years after publication
• Access Criteria: Reasonable scientific proposal approved by the steering committee and execution of a data-sharing agreement