Free for Weaning ECMO vs Respiratory Driven Study (FORWARD)

Monitoring of Occlusion Pressure and Esophageal Pressure to Guide Weaning From Venovenous ECMO in ARDS: a Randomized Controlled Study

In its most severe form, Acute Respiratory Distress Syndrome (ARDS) may require the use of veno-venous ECMO (vvECMO). While the criteria for vvECMO indication, ECMO settings, and ventilator management are relatively well-defined after the publication of the EOLIA trial and subsequent national or international guidelines, few studies have assessed the criteria and methods for weaning from vvECMO. Besides, advances in the understanding of the pathophysiology of mechanical ventilation (MV) weaning process have led to the development of specific monitoring tools for this phase.

Schematically, respiratory drive can be evaluated via the ventilator by measuring the pressure generated during a 100-millisecond expiratory occlusion (P0.1) and respiratory efforts through the measurement of esophageal pressure variation (delta Poeso).

Recent retrospective studies conducted on COVID-19 ARDS patients supported by vvECMO suggest a longer duration of mechanical ventilation for patients whose weaning and decannulation process was "forced," i.e., performed under conditions of significant respiratory drive and effort. High values of P0.1 and delta Poeso were associated with prolonged MV duration. Self-inflicted lung injury (P-SILI) and elevated transpulmonary pressure related to these uncontrolled respiratory efforts likely explain the negative impact on MV duration.

Therefore, this randomized study proposes to assess these monitoring tools, which are regularly used in clinical practice, to guide vvECMO weaning and decannulation decisions.

Study Overview

• Status: Recruiting
• Conditions: ARDS (Acute Respiratory Distress Syndrome)
• Intervention / Treatment: Other: P0.1 and delta Poeso integration into the decanulation decision

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sami HRAIECH, M.D., Ph.D; Phone Number: +33 04 91 96 58 35; Email: sami.hraiech@ap-hm.fr
• Study Contact Backup: Name: Christophe GUERVILLY, M.D.; Phone Number: +33 04 91 96 58 35; Email: christophe.guervilly@ap-hm.fr

Study Locations

• France
  • Lyon, France
    • Recruiting
    • Hospices Civiles de Lyon
    • Contact: Jean-Christophe RICHARD, M.D, Ph.D; Email: j-christophe.richard@chu-lyon.fr
  • Marseille, France, 13005
    • Recruiting
    • Assistance - Publique Hôpitaux de Marseille
    • Contact: Christophe GUERVILLY, M.D.; Phone Number: +33 04 91 96 58 35; Email: christophe.guervilly@ap-hm.fr
    • Contact: Sami HRAIECH, M.D, Ph.D.; Phone Number: +33 04 91 96 58 35; Email: sami.hraiech@ap-hm.fr
    • Principal Investigator: Sami HRAIECH, M.D, Ph.D.
    • Sub-Investigator: Christophe GUERVILLY, M.D.
  • Nice, France
    • Recruiting
    • CHU de Nice
    • Contact: Denis DOYEN, M.D; Email: doyen.d@chu-nice.fr
  • Paris, France
    • Recruiting
    • Assistance Publique - Hôpitaux de Paris
    • Contact: Matthieu SCHMIDT, M.D, Ph.D; Email: matthieu.schmidt@aphp.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients aged 18 years or older Patient whose trusted person has given consent for participation in the study
• Patient on veno-venous ECMO with weaning criteria, including:
• Resolution of the cause of ARDS
• Absence of hemodynamic instability, defined as norepinephrine dose ≤ 0.5 μg/kg/min for at least 3 hours
• Use of a ventilatory mode that allows spontaneous ventilation (VS-AI, BiPAP, or APRV)
• Maximum inspiratory pressure ≤ 28 cm H2O, with a maximum driving pressure ≤ 15 cm H2O, enabling tidal volumes between 4 and 8 ml/kg of predicted body weight (PBW)
• ECMO membrane sweep flow ≤ 2 L/min
• Patient protected by social security

Exclusion Criteria:

• Contraindication to the placement of an esophageal pressure balloon (e.g., esophageal varices, nasal trauma, uncontrolled coagulopathy, severe thrombocytopenia),
• Patient with treatment limitation at the time of inclusion,
• Patient in the time frame of exclusion from another research protocol at the time of consent signing,
• Vulnerable patients: minor, adult patient under guardianship or curatorship, patient deprived of liberty, pregnant or breastfeeding woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ECMO-physio group; Patients undergo the ultimate vvECMO weaning test with minimal ECMO support (ECMO flow ≤ 3 L/min, fresh gas flow ≤ 1 L/min, FiO2 21%) and mechanical ventilation with partial support, allowing spontaneous ventilation. P0.1 and delta Poeso values will be monitored and integrated into the decannulation decision	Other: P0.1 and delta Poeso integration into the decanulation decision; P0.1 and delta Poeso integration into the decanulation decision
No Intervention: ECMO-gazo group; Patients undergo the ultimate vvECMO weaning test with minimal ECMO support, similar to the experimental group. P0.1 and delta Poeso values will be monitored in a blinded manner by an independent investigator and will not be integrated into the decannulation decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation from ECMO decannulation to weaning from mechanical ventilation	The weaning from mechanical ventilation is defined as the absence of mechanical ventilation for 48 consecutive hours.	60 days after inclusion
P0.1 and delta Poeso measurements	P0.1 and delta Poeso values will be monitored and tracked at inclusion and then every 8 hours until decannulation, and up to 48 hours after decannulation. In the experimental group, these values will be incorporated into the criteria guiding the decannulation decision. In the control group, these values will be monitored and recorded by an investigator who is not involved in the decannulation decision. These values will not be included in the criteria guiding the decannulation decision.	From inclusion to 48h after decanulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate in intensive care unit		60 days after inclusion
Mortality rate in hospital		60 days after inclusion
Intensive care unit stay duration from inclusion		60 days after inclusion
Hospital stay duration from inclusion		60 days after inclusion
Total number of days spent on ECMO from admission to intensive care unit discharge		60 days after inclusion
Total duration of mechanical ventilation		60 days after inclusion
Time between the start of mechanical ventilation and ECMO cannulation		60 days after inclusion
Number of ventilator-free days		60 days after inclusion
Number of patients decannulated and then re-initiated on vvECMO		60 days after inclusion
Number of patients requiring controlled ventilation for at least 24 hours after decannulation		60 days after inclusion
Number of days with continuous sedation with or without continuous paralysis after decannulation		60 days after inclusion
Incidence of barotrauma assessed by radiographs and clinical examination after decannulation		60 days after inclusion
Percentage of patients placed in prone positioning after decannulation		60 days after inclusion
Number of days on inhaled nitric oxide after decannulation		60 days after inclusion
Number of patients who received corticosteroid therapy	≥ 0.5 mg/kg of equivalent methylprednisolone	60 days after inclusion
Neuromyopathy on the day of decannulation	Neuromyopathy will be assessed using the Medical Research Council score. Total score ranges from 0 (complete tetraplegia) to 60 (normal muscle strength).	Day of decanulation
Neuromyopathy on the day of weaning from mechanical ventilation	Neuromyopathy will be assessed using the Medical Research Council score. Total score ranges from 0 (complete tetraplegia) to 60 (normal muscle strength).	Day of weaning from mechanical ventilation

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François Crémieux, assistance publique - hôpitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 14, 2025

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Decannulation; veno-venous ECMO
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Injury; Acute Lung Injury
• Other Study ID Numbers: RCAPHM23_0464; ID-RCB (Other Identifier: 2025-A02583-46)

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
• product manufactured in and exported from the U.S.: No