Ventilation of the Extremely Premature Infants Optimized by Dead Space Washout (Volem)

Open Randomised Study of Conventional Ventilation Optimised by Dead Space Washout in Extremely Premature Infants

The Continuous Tracheal Gas Insufflation (CTGI) is a ventilation option of conventional mechanical ventilation that is used to reduce or even eliminate the dead space caused by respiratory prostheses. This objective is of particular interest in the smallest preterm infants, where the volume of anatomical dead space due to prostheses is little different from the tidal volume. The principle of this option is to continuously blow an additional flow of 0.2 L/minute at the tip of the endotracheal tube to purge expired CO2 trapped in the prostheses, to have a CO2-free volume of gas available for subsequent insufflation.

The goal of this clinical trial is to learn if Continuous Tracheal Gas Insufflation (CTGI) works to reduce ventilatory dependence in preterm infants after mechanical ventilation. It will also learn about the safety of CTGI. The main questions it aims to answer are:

• Does Continuous Tracheal Gas Insufflation (CTGI) reduce the number of days of non-invasive ventilation in extremely preterm infants who needed mechanical ventilation?
• Does Continuous Tracheal Gas Insufflation (CTGI) reduce the age at the weaning of any ventilatory support and/or oxygen supplementation.

Researchers will compare the clinical outcome of patients mechanically ventilated with the CTGI-device to the outcome of patients ventilated without the CTGI device, to see if the CTGI ventilation works to reduce ventilation dependence.

Participants will:

• Be mechanically ventilated using CTGI (if randomly assigned in the CTGI-group), for the entire endotracheal ventilation period during their stay in the neonatal intensive care unit.

Study Overview

• Status: Not yet recruiting
• Conditions: Ventilator-Induced Lung Injury; Medical Device; Extremely Low Birthweight Infant; Continuous Tracheal Gas Insufflation; Lung Protection
• Intervention / Treatment: Device: Ventilation with Dead Space Washout via Continuous Tracheal Gas Insufflation (CTGI)

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claude Danan, M.D.; Phone Number: +33609187562; Email: claude.danan@chicreteil.fr
• Study Contact Backup: Name: Camille Jung, MD, PhD; Phone Number: +33157022268; Email: camille.jung@chicreteil.fr

Study Locations

• France
  • Creteil, France, 94010
    • Centre Hospitalier Intercommunal de Créteil
    • Contact: Fabrice Decobert, MD; Phone Number: +33; Email: fabrice.decobert@chicreteil.fr
    • Contact: laurence caeymaex, MD PhD; Phone Number: +33664095607; Email: laurence.caeymaex@gmail.com
    • Contact: Fabrice Decobert, MD
  • Nantes, France, 44000
    • Centre Hospitalier Universitaire de Nantes
    • Contact: Cyril Flamant, MD PhD; Phone Number: +33240083483; Email: cyril.flamant@chu-nantes.fr
    • Contact: Geraldine Apprioual, MD; Phone Number: +33240083483; Email: geraldine.apprioual@chu-nantes.fr
    • Contact: cyril flamant, MD PhD
  • Paris, France, 75014
    • Centre Hopistalier Universitaire Cochin Port Royal aphp
    • Contact: Juliana Patkai, MD; Phone Number: +33158413645; Email: juliana.patkai@aphp.fr
    • Contact: Juliana Patkai, MD
  • Paris, France, 75019
    • Centre hospitalier Robert Debré aphp
    • Contact: Valerie Biran, MD PhD; Phone Number: +33140034191; Email: valerie.biran@aphp.fr
    • Contact: Nizar Khattat, MD; Phone Number: +33140031331; Email: nizar.khattat@aphp.fr
    • Contact: valerie biran, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gestational Age at birth between 23 weeks gestation + 0 days and 26 weeks gestation + 6days
• Age between 0 and 7 days of life
• Need for intubation and mechanical ventilation before day 8 of life
• Availability of the Research-associated medical devices
• Beneficiary of a social security system (in France: CMU or securité sociale)
• Parental consent for their infant to participate in this trial

Exclusion Criteria:

• Known Severe Congenital Malformation (potential life-threatening malformation)
• Known Preexisting Severe Intraventricular Haemorrhage (grade 3 or 4) and/or other brain abnormality that can alter life prognosis
• Known Genetic Disorder (potential life-threatening malformation)
• Preexistent mechanical ventilation for a duration of more than 12 hours
• Participation in another interventional research trial before inclusion

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: Continuous Tracheal Gas Insufflation; the preterm infant intubated and ventilated with Continuous Tracheal Gas Insufflation	Device: Ventilation with Dead Space Washout via Continuous Tracheal Gas Insufflation (CTGI); The intervention involves adding a device which allows CTGI (the "CTGI-device") to washout the dead space in preterm mechanically ventilated infants. Dead space washout using the CTGI-device is an option added to standard ventilation, to reduce or even cancel anatomical dead space due to respiratory prostheses in intubated preterm infants.; Other Names: Continuous Tracheal Gas Insufflation; CTGI
No Intervention: Standard ventilation without CTGI; In the No Intervention arm, the preterm infants are mechanically ventilated using standard ventilation, without the CTGI-device. There is no dead space washout.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative duration of all periods of non-invasive ventilation	The cumulative duration of all periods of non-invasive ventilation, in days, starting from birth, and up to maximum 45 weeks corrected gestational age. Non-invasive ventilation includes all types of positive pressure support non-invasive ventilation and high flow nasal cannula ventilation (HFNC).	From birth to the end of hospital stay, up to maximum 45 weeks of corrected gestational age.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants deceased	For each arm: mortality rate during initial hospitalization.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Measure of the Driving Pressure during mechanical ventilation	Mean Driving pressure (∆P: Ppeak-PEEP) collected each 12 hours for all patients on invasive mechanical ventilation.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Measure of expiratory tidal volume during mechanical ventilation.	Mean expiratory tidal volume (VT) collected each 12 hours for all patients on invasive mechanical ventilation.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Measure of carbon dioxide partial pressure (PCO2) on blood gas	Carbon dioxide partial pressure (PCO2) on patient's blood gas during mechanical ventilation	From enrollment up to maximum 15 days of life
Measure of Transcutaneous Carbon dioxide partial pressure (TcPCO2)	Transcutaneous measure of Carbon dioxide partial pressure (TcPCO2) collected each 12 hours during mechanical ventilation.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants who received a second dose of surfactant	Rates of patients with more than one dose of surfactant replacement therapy.	From birth up to maximum 7 days of life.
Number of participants treated with high-frequency ventilation (HFV) or high-frequency oscillatory ventilation (HFOV).	Rates of patients treated with High Frequency ventilation (HFV) or High frequency oscillatory ventilation (HFOV) during invasive mechanical ventilation.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Use of Inhaled Nitric Oxide (iNO therapy)	Rates of patients treated with nitric oxyde (iNO) during invasive mechanical ventilation.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participant with Severe hypoxemia	Rates of patients with Oxygenation Index ≥ 10	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants treated for Pneumothorax	Rates of patients with treated Pneumothorax (Needle Thoracentesis or Chest Drainage)	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants treated with Systemic Corticosteroids for Prevention or Management of Bronchopulmonary Dysplasia (BPD)	Rates of patients treated with systemic corticosteroids for the prevention or management of BPD and number of days of treatment, excluding prophylactic hydrocortisone treatment in the first 10 days of life.	From enrollment to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants diagnosed as Bronchopulmonary Dysplasia (BPD)	Rates of patients with Bronchopulmonary Dysplasia (BPD) diagnosed at 36 weeks of corrected gestational age.	From two days before 36 weeks of corrected gestational age until two days after 36 weeks of corrected gestational age..
Number of participants with unplanned extubation	Rates of unplanned extubations per 100 ventilator days, and context.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Calculation of days with invasive mechanical ventilation for each participant.	Number of days spent on invasive mechanical ventilation	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Calculation of the mean age at definitive weaning from invasive ventilation for the participants in each arm.	Age at total weaning from invasive mechanical ventilation	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Age of participants at definitive weaning from all positive pressure ventilatory support	The age in days when the infant is definitively weaned from invasive and non-invasive positive pressure ventilation, excluding High Flow Nasal Canula (HFNC) and Low Flow Nasal Canula ventilation (LFNC).	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Age of the participants at the definitive withdrawal of any Ventilatory Support	The age in days when the infant is definitively weaned from invasive and non-invasive ventilation, including High-Flow Nasal Cannula (HFNC). This excludes Low-Flow Nasal Cannula (LFNC), with or without supplemental oxygen delivery.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Age of the participants at definitive O2 weaning.	The age in days when the patient is definitively weaned from oxygen supplementation. This includes being weaned from any respiratory support system, as well as from Low-Flow Nasal Cannula, with or without supplemental oxygen delivery.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants with Late-onset primary bloodstream infections	Rates of Late-onset primary bloodstream infections using CDC surveillance definitions, calculated for 1000 central-line days.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants with Neuroimaging complications	Rates of acquired neuroimaging complications: Periventicular Leucomalacia, Cerebellar haemorrhage, Intra-Ventricular Haemorrhage Grade 3 and 4.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Number of participants Treated for Retinopathy (ROP)	Rates of Retinopathy (ROP) receiving either retinal laser or intravitreal anti-VEGF therapy.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Number of days for each participant of Exposure to systemic analgesic or sedatives treatments	Number of days with systemic analgesic or sedative treatments.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
First cytokine dosage in tracheal aspirates.	Mean Cytokines dosage from tracheal aspirates in intubated patients (one unique aspiration). This outcome will be assessed only for patients enrolled in the study and on mechanical ventilation between 24 and 48 hours of life.	Between 24 hours to 48 hours of life.
Second cytokine dosage in tracheal aspirates.	Mean Cytokines dosage from tracheal aspirates in intubated patients (one unique aspiration). This outcomes will be assessed only for patients enrolled in the study and on mechanical ventilation between day 4 and 5 of life.	Between day 4 to day 5 of life.
Third cytokine dosage in tracheal aspirates.	Mean Cytokines dosage from tracheal aspirates in intubated patients. This outcomes will be assessed only for patients enrolled in the study and on mechanical ventilation between day 10 and day 12 of life.	Between day 10 to day 12 of life.
Number of participants requiring hemodynamic support.	Rates of patients receiving hemodynamic support during their hospital stay (systemic catecholamines, volume expansion).	From enrollment in the study to the date of the end of the hospital stay, up to maximum 5 months of life
Measurement of average weight gain for all study participants in each arm.	Weight gain in grams between birth weight and weight at 36 weeks of corrected gestational age.	From birth to the date of 36 weeks of corrected gestational age.
Number of days for each participant in the study with central venous line	Addition of all the periods the patients has a central line, in days.	From birth to the date of the end of the hospital stay, up to maximum 5 months of life
Resuts of Neurodevelopmental Follow-up for surviving participants.	Results of the validated French version of the "Ages & stages questionnaires" (ASQ3), a developmental screening tool based on parental reporting for their child. This tool will be sent to the parents, and collected.	At 2 years of corrected age (± 2 months)
Number of participants with Cerebral Palsy	Rates of patients with cerebral palsy.	At 2 years of corrected age (± 2 months)
Number of participants with visual disorders at 2 years of age	Rates of patients with severe visual disorders defined as a need for glasses at 2 years of corrected age (± 2 months)	At 2 years of corrected age (± 2 months)
Number of participants necessitating respiratory drugs during the two first years of life.	Rates of patients with respiratory symptoms in the first two years, defined as the need for respiratory medications (inhaled or systemic) at any time in this period.	From the date of discharge from the hospital to 2 years of age

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil
• Investigators: Principal Investigator: Juliana PATKAI, MD, CHU Cochin-Port Royal; Principal Investigator: Valérie BIRAN, MD, PhD, CHU Robert Debré; Principal Investigator: Cyril FLAMANT, MD, PhD, Nantes University Hospital; Principal Investigator: Fabrice DECOBERT, MD, CHI de Créteil

Study record dates

Study Major Dates

• Study Start (Estimated): February 13, 2025
• Primary Completion (Estimated): April 2, 2027
• Study Completion (Estimated): April 3, 2029

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: mechanical ventilation; Ventilator-Induced Lung Injury; lung protection; extremely low birthweight infant
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Weight; Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Birth Weight; Lung Injury; Ventilator-Induced Lung Injury
• Other Study ID Numbers: Volem

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: Yes
• product manufactured in and exported from the U.S.: Yes