Early Versus Deferred De-escalation From Controlled Ventilation After a 48-Hour Landmark of Physiological Stability

NCT07804992 | Completed DMC

• 1 other identifier: 2025301
• Study Type: observational
• Target: 12,736
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective target trial emulation evaluates the optimal timing of de-escalation from controlled to assisted mechanical ventilation in critically ill adults. Using the clone-censor-weight (CCW) estimator with stabilised inverse-probability-of-censoring weights, we compare two strategies over a 24-hour grace window following a 48-hour landmark: early de-escalation (step-down in ventilatory support mode or successful extubation) versus deferred de-escalation (support maintained or increased). The primary outcome is 28-day in-hospital mortality. Secondary outcomes are 28-day restricted mean survival time (RMST) and ventilator-free days (VFD28). The study uses MIMIC-IV v2.2 (derivation cohort, n=1,902 analysable) with external validation in eICU-CRD v2.0 (validation cohort, n=10,957 analysable). All analyses employ stabilised IPCW with bootstrap confidence intervals, including six sensitivity and robustness analyses (extended covariate adjustment, alternative weight truncation, doubly robust AIPW estimator) and an exploratory FiO₂×PEEP threshold grid.

Conditions

Critical Illness; Respiratory Failure; Mechanical Ventilation

Keywords

mechanical ventilation; ventilator weaning; target trial emulation; critical care

Outcome Measures

Primary Outcomes (1)

• 28-Day In-Hospital Mortality

  Death in hospital within 28 days of ICU admission

  within 28 days of ICU admission

Secondary Outcomes (2)

• 28-Day Restricted Mean Survival Time (RMST)

  within 28 days of ICU admission

• Ventilator-Free Days at Day 28 (VFD28)

  within 28 days of ICU admission

Study Arms (2)

Early De-escalation,Experimental

Step-down in ventilatory support level by Day 3 (transition from controlled to assisted/spontaneous mode, or successful extubation with recorded end of mechanical ventilation while alive)

Other: Ventilatory Support De-escalation Strategy

Deferred De-escalation,Active Comparator

Ventilatory support level maintained or increased between Day 2 and Day 3

Other: Ventilatory Support De-escalation Strategy

Interventions

Ventilatory Support De-escalation Strategy OTHER

The study compares two respiratory support management strategies over a 24-hour grace window (Day 2 to Day 3 of ICU admission) following the 48-hour landmark. Early De-escalation: Ventilatory support level is decreased, defined as a transition from a controlled mode to an assisted/spontaneous mode, or successful extubation (end of mechanical ventilation) while the patient is alive by Day 3. Deferred De-escalation: Ventilatory support level is maintained or increased between Day 2 and Day 3.

Deferred De-escalation,Active Comparator; Early De-escalation,Experimental

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

Adults admitted to the intensive care unit (ICU) receiving invasive mechanical ventilation who are alive and ventilated at the 48-hour landmark with low respiratory support requirements (FiO₂ ≤50%, PEEP ≤10 cmH₂O).

You may qualify if:

• Age ≥18 years
• Invasive mechanical ventilation for \>24 hours
• Alive and still ventilated at 48 hours after ICU admission
• Classifiable Day-2 ventilatory mode (controlled or assisted/spontaneous)
• Day-2 FiO₂ ≤50%
• Day-2 PEEP ≤10 cmH₂O

You may not qualify if:

• Death during the 24-hour grace period (Day 2 to Day 3)
• Unascertainable Day-3 strategy (missing mode without documented ventilation end)

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Department of Critical Care Medicine，Ruijin Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai，China.

Shanghai, Shanghai Municipality, 200025, China

Location

Related Publications (2)

• Pollard TJ, Johnson AEW, Raffa JD, Celi LA, Mark RG, Badawi O. The eICU Collaborative Research Database, a freely available multi-center database for critical care research. Sci Data. 2018 Sep 11;5:180178. doi: 10.1038/sdata.2018.178.

  PMID: 30204154 RESULT

• Hernan MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. Am J Epidemiol. 2016 Apr 15;183(8):758-64. doi: 10.1093/aje/kwv254. Epub 2016 Mar 18.

  PMID: 26994063 RESULT

MeSH Terms

Conditions

Critical Illness; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 4, 2026
• Study Start: January 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: August 31, 2026
• Last Updated: September 4, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE

Locations

CN (1)