Time-controlled Adaptive Ventilation (TCAV) Compared With Conventional Ventilation in Patients With Moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) Secondary to Community-acquired Pneumonia (EARLY-TCAV)

Efficacy and Safety of Time-controlled Adaptive Ventilation (TCAV) Compared With Conventional Ventilation in Patients Requiring Invasive Ventilation for Moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) Secondary to Community-acquired Pneumonia

ARDS is a pathology with mortality rates reaching 40%. Invasive ventilation, the cornerstone of ARDS management, leads to "ventilation-induced lung injury" (VILI). An approach based on pressure-controlled ventilation with unassisted spontaneous respirations (PC-SV or APRV) can limit the occurrence of VILI. Time-controlled adaptive ventilation (TCAV) is based on high mean inspiratory airway pressure, while limiting expiratory time at low pressure. TCAV has shown positive effects in experimental and observational studies. However, its efficacy and safety in patients with moderate-to-severe ARDS remains to be evaluated.

Evaluation of the efficacy of early application of TCAV compared to standard ventilation on the severity of alveolar damage leading to injury-related pulmonary edema in patients with moderate to severe ARDS After obtaining patient's consent, eligible patients will be included in this open-label, randomized controlled pilot study with stratification by minimization based on initial severity. The experimental group will be the TCAV group, where ventilator settings will be standardized. The ventilator in the standard care group will be set to volumetric mode with positive end-expiratory pressure according to the EXPRESS protocol.

The measurement of extravascular lung water will be compared on day 2 between the TCAV settings group and the standard care settings group using the PICCO system.

The TCAV setting is simple and inexpensive. In ARDS patients, the increase in injury-related pulmonary edema is a relevant marker of mortality, and its reduction could improve patients' outcomes. Our study aims to evaluate the efficacy and safety of these settings to justify a future large-scale, multicenter randomized trial.

Study Overview

• Status: Not yet recruiting
• Conditions: ARDS (Acute Respiratory Distress Syndrome)
• Intervention / Treatment: Other: Invasive ventilation with the Time-controlled Adaptative Ventilation settings applied to the Airway Pressure Release Ventilation mode; Other: Volume Control

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthieu KOSZUTSKI, MD; Phone Number: +33 3 83 15 30 17; Email: m.koszutski@chru-nancy.fr

Study Locations

• France
  • Nancy, France, 54000
    • Chru de Nancy
    • Contact: Matthieu KOSZUTSKI, MD; Phone Number: +33 3 3 83 15 30 17; Email: m.koszutski@chru-nancy.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Intensive care unit hospitalisation for ARDS with a PaO₂/FiO₂ ratio ≤ 200 mmHg and PEEP ≥ 5 cmH₂O under invasive ventilation
• Criteria for community-acquired pneumonia, 2 of the following: cough, purulent sputum, chest pain, dyspnea
• Onset of symptoms ≤ 7 days
• Invasive ventilation initiated ≤ 24 hours
• Affiliation to a social security program
• Patient for whom written consent has been obtained from a trusted person or a family member, or inclusion in a situation of immediate life-threatening emergency

Exclusion Criteria:

• Focal ARDS defined as unilateral involvement (1 out of 4 quadrants or 2 on the same side) on imaging (chest X-ray or CT scan)
• Right heart failure not related to acute pulmonary heart disease secondary to ARDS (pulmonary embolism, myocarditis, ischemic cause)
• Pneumothorax, drained or undrained, with a persistent pleural air leak
• COPD with significant obstructive impairment defined by the presence of chronic respiratory disease and oxygen therapy or non-invasive ventilation at home
• Circulatory support via VV-ECMO or VA-ECMO
• Presence of a patent foramen ovale
• Active limitation of therapies
• Increased intracranial pressure
• Sickle cell disease
• Burns > 30%
• Expected invasive mechanical ventilation for less than 48 hours
• A person covered by Articles L. 1121-5, L. 1121-7, and L. 1121-8 of the French Public Health Code
• Pregnant or breastfeeding women
• A not emancipated minor
• Adults subject to legal protective measures (guardianship, conservatorship, judicial protection) or inability to give consent
• Persons deprived of liberty by a judicial or administrative decision, persons receiving psychiatric care pursuant to Articles L. 3212-1 and L. 3213-1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Time-controlled Adaptative Ventilation; Invasive ventilation with the ventilator set on the Airway Pressure Release Ventilation mode.	Other: Invasive ventilation with the Time-controlled Adaptative Ventilation settings applied to the Airway Pressure Release Ventilation mode; Invasive ventilation with the ventilator set on the Airway Pressure Release Ventilation mode as follows: high pressure: initially set at the level of the plateau pressure of the volume control mode; low pressure: set at 0 cmH2O (mandatory); time high: initially set at 3 seconds; time low: set to terminate the expiratory flow at 75% of peak expiratory flow; slope: 0
Active Comparator: Volume Control; Invasive ventilation with the ventilator set on the Volume control mode.	Other: Volume Control; Invasive ventilation with the ventilator set on the Volume control mode as follows: Tidal volume (VT) set at 6 ml/kg of predicted body weight; Positive end-expiratory pressure (PEEP) set according to the low PEEP/FiO2 table

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extravascular Lung Water (EVLW)	Measured with transpulmonary thermodilution (TPTD) and expressed in ml per kilogram of body weight	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Occurrence of death	60 days
Ventilator-free days	Number of days without invasive or non-invasive ventilation	day 30
Major Adverse Kidney Events (MAKE)	Need of dialysis, decrease ≥ 25% of glomerular filtration rate and all cause-death	Day 7, Day 30
Adverse Events	Defined as: Worsening hypoxemia (increase in FiO₂ of more than 40%) within the first 30 minutes after randomization; Development of a pneumothorax with a persistent air leak; Persistent hemodynamic instability; Cardiac Index < 2 L/min/m²,; Increase in norepinephrine bitartrate dose > 1 µg/kg/min; Persistent acute cor pulmonale; Presence of a patent foramen ovale during the first 48 hours after randomization; Severe Hypoxemia; Severe Acidosis and low tidal volume in the TCAV group; Implementation of VV-ECMO or VA-ECMO; Tidal volumes exceeding 8 mL/kg of ideal body weight	Day 30
Pressure difference	in cmH20	day 1, day 2, day 3, day 4
Extravascular Lung Water Indexed to the predicted body weight (EVLWIp)	Measured with transpulmonary thermodilution (TPTD) and expressed in ml per kilogram of predicted body weight	48 hours

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ARDS; APRV; Invasive ventilation; TCAV
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Injury; Acute Lung Injury
• Other Study ID Numbers: 2024PI147

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