Critical IllnessNCT07804992
Early Versus Deferred De-escalation From Controlled Ventilation After a 48-Hour Landmark of Physiological Stability
An observational study of Critical Illness and Respiratory Failure, run by Ruijin Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Respiratory Failure, Mechanical Ventilation
- What is being tested?
- Ventilatory Support De-escalation Strategy
- How many people
- 12,736 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2024to 31 Aug 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
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: 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).
Who may be able to join
- 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
Who cannot join
- Death during the 24-hour grace period (Day 2 to Day 3)
- Unascertainable Day-3 strategy (missing mode without documented ventilation end)
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Critical Care Medicine，Ruijin Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai，China.
Shanghai, Shanghai Municipality, 200025
About this study
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.
Read the detailed description
Background: Mechanical ventilation is life-saving, yet optimal timing of transition from controlled to assisted modes remains uncertain. Prolonged controlled ventilation exposes patients to sedation, diaphragm dysfunction, and lung injury, while premature de-escalation risks asynchrony and reintubation.
Design: Landmark target trial emulation with 48-hour eligibility ascertainment.
Eligibility: Adults ≥18 years, invasive mechanical ventilation >24 hours, alive and ventilated at 48 hours with classifiable Day-2 mode (controlled or assisted), Day-2 FiO₂ ≤50%, Day-2 PEEP ≤10 cmH₂O.
Strategies: Early-support level decreased by Day 3 (mode step-down from controlled to assisted, or successful extubation while alive); Deferred-support maintained or increased.
Analysis: Single-interval CCW estimator with stabilised IPCW (truncated 1st-99th percentile), propensity model with 21 baseline covariates, bootstrap 95% CIs (2,000 resamples primary; 800 sensitivity). Sensitivity analyses: no truncation, ICU mortality, unweighted per-protocol, extended 40-covariate adjustment, 5th-95th truncation, AIPW doubly robust estimator. E-values computed for unmeasured confounding.
External validation: Harmonised protocol in eICU-CRD v2.0 (208 hospitals, n=10,957), outcome: in-hospital mortality.
- Being tested
- Ventilatory Support De-escalation Strategy
- Keywords
- mechanical ventilation, ventilator weaning, target trial emulation, critical care
- Medical subject headings
- Critical Illness, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ventilatory Support De-escalation StrategyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Other: Ventilatory Support De-escalation Strategy | |
| Deferred De-escalation,Active Comparator | Ventilatory support level maintained or increased between Day 2 and Day 3 Receives: Other: Ventilatory Support De-escalation Strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-Day In-Hospital Mortality
Death in hospital within 28 days of ICU admission
Measured: within 28 days of ICU admission
Secondary outcomes (2)
28-Day Restricted Mean Survival Time (RMST)
Mean survival time up to 28 days
Measured: within 28 days of ICU admission
Ventilator-Free Days at Day 28 (VFD28)
Number of days alive and free of mechanical ventilation within the first 28 days; set to zero for patients who died before day 28
Measured: within 28 days of ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2026
- Study start1 Jan 2024
- Primary completion31 Dec 2025
- Study completion31 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 12,736 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07804992
- Sponsor's protocol ID
- 2025301
- Status last verified
- Aug 2026
- First submitted
- 1 Sep 2026
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 30204154Hernan 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.
PubMed 26994063
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Versus Deferred De-escalation From Controlled Ventilation After a 48-Hour Landmark of Physiological Stability
- ClinicalTrials.gov ID
- NCT07804992
- Acronym / sponsor ID
- 2025301
- Keywords
- mechanical ventilation, ventilator weaning, target trial emulation, critical care
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12,736 participants (actual)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Aug 2026 (actual)
- First posted
- 4 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background: Mechanical ventilation is life-saving, yet optimal timing of transition from controlled to assisted modes remains uncertain. Prolonged controlled ventilation exposes patients to sedation, diaphragm dysfunction, and lung injury, while premature de-escalation risks asynchrony and reintubation.
Design: Landmark target trial emulation with 48-hour eligibility ascertainment.
Eligibility: Adults ≥18 years, invasive mechanical ventilation >24 hours, alive and ventilated at 48 hours with classifiable Day-2 mode (controlled or assisted), Day-2 FiO₂ ≤50%, Day-2 PEEP ≤10 cmH₂O.
Strategies: Early-support level decreased by Day 3 (mode step-down from controlled to assisted, or successful extubation while alive); Deferred-support maintained or increased.
Analysis: Single-interval CCW estimator with stabilised IPCW (truncated 1st-99th percentile), propensity model with 21 baseline covariates, bootstrap 95% CIs (2,000 resamples primary; 800 sensitivity). Sensitivity analyses: no truncation, ICU mortality, unweighted per-protocol, extended 40-covariate adjustment, 5th-95th truncation, AIPW doubly robust estimator. E-values computed for unmeasured confounding.
External validation: Harmonised protocol in eICU-CRD v2.0 (208 hospitals, n=10,957), outcome: in-hospital mortality.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early De-escalation,Experimental | – | Other: Ventilatory Support De-escalation StrategyStep-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) |
| Deferred De-escalation,Active Comparator | – | Other: Ventilatory Support De-escalation StrategyVentilatory support level maintained or increased between Day 2 and Day 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (6 listed)
- 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%
Key exclusion criteria (2 listed)
- Death during the 24-hour grace period (Day 2 to Day 3)
- Unascertainable Day-3 strategy (missing mode without documented ventilation end)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ventilatory Support De-escalation StrategyThe 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. | Other | Deferred De-escalation,Active Comparator, Early De-escalation,Experimental |
Primary outcome
28-Day In-Hospital Mortality
Time frame: within 28 days of ICU admission
Death in hospital within 28 days of ICU admission
2 secondary outcomes
28-Day Restricted Mean Survival Time (RMST)
Time frame: within 28 days of ICU admission
Ventilator-Free Days at Day 28 (VFD28)
Time frame: within 28 days of ICU admission
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Results publication: PubMed 30204154Pollard 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.
- Results publication: PubMed 26994063Hernan 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Critical Illness and Respiratory Failure, run by Ruijin Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28-Day In-Hospital Mortality (time frame: within 28 days of ICU admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07804992, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.