Open Lung Maneuvers During High Frequency Oscillatory Ventilation in Preterm Infants (OPEN4HFOV)

Open Lung Maneuvers During High Frequency Oscillatory Ventilation in Extremely Preterm Infants - A Single Center Randomized Controlled Trial

To assess whether stepwise oxygenation-guided lung recruitment at regular intervals reduces the oxygen saturation index (OSI = Mean Airway Pressure × Fraction of inspired Oxygen × 100 / peripheral Oxygen Saturation, OSI = MAPxFiO2x100/SpO2) averaged over high frequency oscillation ventilation (HFOV) time in extremely preterm infants.

Study Overview

• Status: Recruiting
• Conditions: Lung Injury, Acute; Extreme Prematurity; High Frequency Oscillation Ventilation
• Intervention / Treatment: Procedure: regular lung recruitment

Detailed Description

Background: Open lung maneuvers aim to recruit and stabilize the majority of collapsed alveoli, using oxygenation as an indirect variable for lung volume. The stepwise oxygenation-guided lung recruitment procedure during frequency oscillatory ventilation (HFOV) in preterm infants has a low risk of lung hyperinflation and air leak syndrome. Nevertheless, open lung maneuvers at regular intervals during HFOV to maintain or restore oxygenation is not implemented as a routine procedure in the neonatal intensive care.

Aim of the study: To assess whether stepwise oxygenation-guided lung recruitment at regular intervals reduces the oxygen saturation index (OSI = Mean Airway Pressure × Fraction of inspired Oxygen × 100 / peripheral Oxygen Saturation, OSI = MAPxFiO2x100/SpO2) averaged over HFOV time in extremely preterm infants.

Study design: Single center randomized controlled study.

Methods: Thirty-six extremely preterm infants below 28 weeks of gestational age and on high frequency oscillation ventilation receive either stepwise oxygenation-guided lung recruitment maneuver at regular intervals (intervention) and upon decision of the care giving team (intervention group) or lung recruitment maneuver only upon decision of the care giving team (standard, control group). The primary outcome is the oxygen saturation index averaged over HFO ventilation time. The observation time of the HFOV will be limited to at most seven days.

Sample size: Fifteen infants need to be enrolled in each group to have 80% power (at a two-sided alpha level of 5%) to detect a difference of 25% in the oxygen saturation index between the intervention group and the control group.

Main outcome variables: Oxygen saturation index averaged over HFO ventilation time.

Secondary outcome variables: Bronchopulmonary dysplasia (BPD); days of ventilation; oxygen saturation index averaged over ventilation time (HFO and conventional ventilation); the following variables measured before, during and after a single stepwise oxygenation-guided recruitment maneuver: echocardiographic parameters, reactance, relative impedance changes, lung ultrasound measurements, transcutaneous partial carbon dioxide (CO2), blood pressure, heart rate.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tobias Werther; Phone Number: +4314040032320; Email: tobias.werther@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Tobias Werther; Phone Number: 014040032320; Email: tobias.werther@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Preterm infants

• born below 28 weeks of gestational age
• not older than 29 weeks of postmenstrual age
• receive HFOV

Exclusion Criteria:

• known congenital anomalies of the heart, of the lung, and/or of the central nervous system
• known chromosomal abnormalities
• participation in other intervention trials

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: Intervention; lung recruitment maneuvers performed every twelve hours during HFOV	Procedure: regular lung recruitment; stepwise oxygenation-guided lung recruitment at regular (twelve hours) intervals during high frequency oscillation ventilation
No Intervention: Control; no regular lung recruitment maneuvers during HFOV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HFOV oxygen saturation index	oxygen saturation index averaged over high frequency oscillation ventilation for not more than seven consecutive days	through study completion, an average 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bronchopulmonary dysplasia	respiratory support at 36 weeks postmenstrual age	through study completion, an average 10 weeks
days of ventilation	days on conventional and high frequency oscillation ventilation	through study completion, an average 10 weeks
overall oxygen saturation index	oxygen saturation index averaged over ventilation time	through study completion, an average 10 weeks

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Tobias Werther, Medical University of Vienna

Publications and helpful links

General Publications

• De Jaegere A, van Veenendaal MB, Michiels A, van Kaam AH. Lung recruitment using oxygenation during open lung high-frequency ventilation in preterm infants. Am J Respir Crit Care Med. 2006 Sep 15;174(6):639-45. doi: 10.1164/rccm.200603-351OC. Epub 2006 Jun 8.
• Rimensberger PC, Pache JC, McKerlie C, Frndova H, Cox PN. Lung recruitment and lung volume maintenance: a strategy for improving oxygenation and preventing lung injury during both conventional mechanical ventilation and high-frequency oscillation. Intensive Care Med. 2000 Jun;26(6):745-55. doi: 10.1007/s001340051242.
• Rimensberger PC, Beghetti M, Hanquinet S, Berner M. First intention high-frequency oscillation with early lung volume optimization improves pulmonary outcome in very low birth weight infants with respiratory distress syndrome. Pediatrics. 2000 Jun;105(6):1202-8. doi: 10.1542/peds.105.6.1202.
• de Waal K, Evans N, van der Lee J, van Kaam A. Effect of lung recruitment on pulmonary, systemic, and ductal blood flow in preterm infants. J Pediatr. 2009 May;154(5):651-5. doi: 10.1016/j.jpeds.2009.01.012.
• Zannin E, Doni D, Ventura ML, Fedeli T, Rigotti C, Dellaca RL, Tagliabue PE. Relationship between Mean Airways Pressure, Lung Mechanics, and Right Ventricular Output during High-Frequency Oscillatory Ventilation in Infants. J Pediatr. 2017 Jan;180:110-115. doi: 10.1016/j.jpeds.2016.09.015. Epub 2016 Oct 10.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 1161/2019

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