Hemodynamic Impact of the Spontaneous Ventilation Test in Patients at Risk of Weaning Pulmonary Oedema (WAPITI 2)

Weaning-induced pulmonary edema (WIPE) from the ventilator is a frequent cause of extubation failure or delay, which prolongs the duration of invasive mechanical ventilation and the associated morbidity and mortality. WIPE is a very frequent cause of extubation failure in at-risk patients. A spontaneous breathing trial (SBT) is performed before extubating a patient, either by disconnecting the patient from the ventilator (T-piece SBT) or by setting the ventilator to spontaneous breathing mode with pressure support at 7 cm H2O and zero positive end-expiratory pressure (PS-ZEEP SBT). There is currently no recommendation regarding which SBT modality should be used, particularly in patients at risk of WIPE. The hemodynamic changes induced by the SBT can lead to WIPE, which typically develops within minutes of the SBT onset.

The hypothesis being tested is that, by altering intrathoracic pressure during the patient's inspiration (negative pressure), the T-piece SBT leads to a greater increase in left ventricular filling pressures compared to the PS-ZEEP SBT.

Study Overview

• Status: Not yet recruiting
• Conditions: Weaning-induced Pulmonary Edema
• Intervention / Treatment: Procedure: T-piece SBT; Procedure: PS-ZEEP SBT

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Ambroise Paré Hospital -APHP
    • Contact: Adrien JOSEPH, MD; Phone Number: 0149095601; Email: adrien.joseph@aphp.fr
    • Principal Investigator: Adrien JOSEPH, MD
  • Limoges, France, 87042
    • Limoges University Hospital
    • Principal Investigator: Philippe VIGNON, MD
    • Contact: Philippe VIGNON, MD; Phone Number: +33 05 55 05 88 41; Email: philippe.vignon@chu-limoges.fr
  • Nice, France, 06000
    • Nice University Hospital - Archet
    • Contact: Mathieu JOZWIAK, MD; Phone Number: +33 0492035510; Email: jozwiak.m@chu-nice.fr
    • Principal Investigator: Mathieu JOZWIAK, MD
  • Nice, France, 06000
    • Nice university hospital - Pasteur
    • Principal Investigator: Denis DOYEN, MD
    • Contact: denis DOYEN, MD+33; Phone Number: 0492033622; Email: denis.doyen@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patient (> 18 years) on invasive mechanical ventilation in the ICU for more than 48 hours
• In the ventilator weaning phase with a first SBT planned
• At risk of WIPE: age over 65 years and/or any type of heart disease and/or chronic respiratory failure and/or obesity

Exclusion Criteria:

• Patient who has already participated in the study
• No transthoracic echocardiographic images suitable for analysis
• Non-sinus rhythm (including pacemaker)
• Tracheostomy
• Chronic neuromuscular or neurodegenerative disease
• Persons deprived of liberty or under legal protection
• Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-piece SBT then PS-ZEEP SBT; In this arm, T-piece SBT will be evaluated first and PS-ZEEP SBT in a second time.	Procedure: T-piece SBT; T-piece SBT will be evaluated first and PS-ZEEP SBT in a second time. If the first SBT fails, regardless of the modality used or the cause of failure, the second SBT will not be performed. The patient will then be managed according to the participating centers' standard of care (treatment guided by the main mechanism of WIPE identified by echocardiography). The two SBTs will be separated by at least 6 hours, during which no therapeutic changes will be made (in case of success at the first SBT). This interval corresponds to the usual SBT schedule (typically one SBT in the morning and one in the afternoon).
Experimental: PS-ZEEP SBT then T-piece SBT; In this arm, PS-ZEEP SBT will be evaluated first and T-piece SBT ina second time.	Procedure: PS-ZEEP SBT; In this arm, PS-ZEEP SBT will be evaluated first and T-piece SBT ina second time. If the first SBT fails, regardless of the modality used or the cause of failure, the second SBT will not be performed. The patient will then be managed according to the participating centers' standard of care (treatment guided by the main mechanism of WIPE identified by echocardiography). The two SBTs will be separated by at least 6 hours, during which no therapeutic changes will be made (in case of success at the first SBT). This interval corresponds to the usual SBT schedule (typically one SBT in the morning and one in the afternoon).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
E/e' ratio	Difference in the percentage change in the averaged E/e' ratio (reflecting changes in left ventricular filling pressures) between the baseline period (just before the start of the SBT) and the end of the SBT (30 minutes if successful, or at the onset of WIPE, whichever occurs first)	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in the averaged E/e' ratio	Comparison between patients according to the modality of the first SBT (T-piece SBT vs. PS-ZEEP SBT) of the absolute change in the averaged E/e' ratio between the baseline period and the end of the SBT	Day1
Absolute change in arterial pressure	The absolute change in arterial pressure between the baseline period and the end of the SBT	day 1
Relative change in arterial pressure	The relative change in arterial pressure between the baseline period and the end of the SBT	Day 1
Number of WIPE cases	The number of WIPE cases	Day 1
Proportion of WIPE cases	The proportion of WIPE cases	Day 1
Number of SBT interruptions	The number of SBT interruptions related to WIPE	Day 1
Absolute change in peak velocity of the mitral E wave	The absolute change in the peak velocity of the mitral E wave at the lateral and septal mitral annulus	Day 1
Relative change in peak velocity of the mitral E wave	The relative change in the peak velocity of the mitral E wave at the lateral and septal mitral annulus	Day 1
Relative change in peak velocity of the mitral e' wave	The relative change in the peak velocity of the mitral e' wave at the lateral and septal mitral annulus	Day 1
Absolute change in peak velocity of the mitral e' wave	The absolute change in the peak velocity of the mitral e' wave at the lateral and septal mitral annulus	Day 1
Absolute change in peak velocity of tricuspid regurgitation	The absolute change in the peak velocity of tricuspid regurgitation	Day 1
Relative change in peak velocity of tricuspid regurgitation	The relative change in the peak velocity of tricuspid regurgitation	Day 1
Number of clinically relevant mitral regurgitation	The number (regurgitant jet area ratio on color Doppler with a maximal Nyquist limit, relative to left atrial area) of clinically relevant mitral regurgitation (≥ grade 2) between the baseline period and the end of the SBT	Day 1
Proportion of clinically relevant mitral regurgitation	The proportion (regurgitant jet area ratio on color Doppler with a maximal Nyquist limit, relative to left atrial area) of clinically relevant mitral regurgitation (≥ grade 2) between the baseline period and the end of the SBT	Day 1
Semi-quantitative assessment of clinically relevant mitral regurgitation	The semi-quantitative assessment (regurgitant jet area ratio on color Doppler with a maximal Nyquist limit, relative to left atrial area) of clinically relevant mitral regurgitation (≥ grade 2) between the baseline period and the end of the SBT	Day 1
Number of dynamic left ventricular outflow tract obstruction	The number (measurement of the maximal systolic gradient on continuous-wave Doppler) of dynamic left ventricular outflow tract obstruction between the baseline period and the end of the SBT	Day 1
Proportion of dynamic left ventricular outflow tract obstruction	The proportion The number (measurement of the maximal systolic gradient on continuous-wave Doppler) of dynamic left ventricular outflow tract obstruction between the baseline period and the end of the SBT	Day 1
Semi-quantitative assessment of dynamic left ventricular outflow tract obstruction	The semi-quantitative assessment (measurement of the maximal systolic gradient on continuous-wave Doppler) of dynamic left ventricular outflow tract obstruction between the baseline period and the end of the SBT	Day 1
Lung ultrasound aeration score	The lung ultrasound aeration score (0 to 3) across all 12 quadrants between the baseline period and the end of the SBT	Day 1
The number of SBTs performed	The number of SBTs performed before extubation	Day 1
The type of SBTs performed	The type of SBTs performed before extubation	Day 1
Duration of such ventilatory support	The Duration of such ventilatory support	Day 1
Number of patients requiring ventilatory support	The number of patients requiring ventilatory support with high-flow oxygen therapy (e.g., Optiflow©) or non-invasive ventilation	Day 1
Number of patients requiring reintubation for mechanical ventilation	The number of patients requiring reintubation for mechanical ventilation within the week following extubation (extubation failure); the day of reintubation, where applicable	Day 7
The number of hours between the second SBT and extubation	The number of hours between the second SBT and extubation	Day 1
Description of the therapeutic changes	A description of the therapeutic changes introduced after the second SBT and before extubation	Day 1
Relative change in hematocrit	The relative change in hematocrit, between the baseline period and the end of the SBT	Day 1
Absolute change in NT-pro-BNP	The absolute change in NT-pro-BNP, between the baseline period and the end of the SBT	Day 1
Absolute change in hematocrit	The absolute change in hematocrit, between the baseline period and the end of the SBT	Day 1
Relative change in NT-pro-BNP	The relative change in NT-pro-BNP, between the baseline period and the end of the SBT	Day 1
Relative change in total plasma protein levels	The relative change in total plasma protein levels, between the baseline period and the end of the SBT	Day 1
Absolute change in total plasma protein levels	The absolute change in total plasma protein levels, between the baseline period and the end of the SBT	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 7, 2029
• Study Completion (Estimated): August 7, 2029

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Weaning-induced pulmonary edema
• Other Study ID Numbers: 87RI25_0075 (WAPITI 2); 2026-A00509-42 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No