Infants with Severe Acute Respiratory Distress Syndrome: the Prone Trial

November 18, 2024 updated by: Tobias Werther, Medical University of Vienna

Short-Term Effect of Prone Positioning in Infants with Severe Acute Respiratory Distress Syndrome

The main objective is to determine the short-term effect of prone positioning in infants with infection-associated severe acute respiratory distress syndrome. The investigators compare oxygenation parameters and measurements from electrical impedance tomography (EIT) and lung ultrasonography (LUS) in mechanically ventilated infants in prone position versus supine position after surfactant administration.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The acute respiratory distress syndrome (ARDS) is an acute lung injury that can be triggered by pulmonary (direct lung injury) and extrapulmonary (indirect lung injury) etiologies. Pediatric ARDS (pARDS) occurs in approximately 3% of children admitted to intensive care units (ICUs) and is associated with approximately 17% mortality. The primary etiologies of pARDS have been summarized as pneumonia (35%), aspiration (15%), sepsis (13%), near-drowning (9%), cardiac disease (7%), and other clinical conditions (21%). ARDS manifests as pulmonary inflammation, alveolar edema, and hypoxemic respiratory failure. Mechanical ventilation remains an essential component in the care of patients with ARDS. Many adjunctive treatments rely on pathophysiological considerations. The pathophysiology of ARDS is characterized by inflammatory, proliferative, and fibrotic phases. The different phases induce a ventilation-perfusion mismatch. Inflammation causes surfactant inactivation and depletion. A number of clinical studies have reported clinical benefits following the instillation of exogenous surfactant in pediatric patients with acute respiratory failure. On the other side, prone positioning seem to be a promising intervention in critically ill infants and children with infection-associated acute lung injury. However, data conflict on the use of prone positioning in pediatric patients with acute lung injury.

Turning patients with moderate to severe lung disease into prone position has shown many positive effects. Prolonged intervals of prone positioning have been associated with a decrease in mortality in adult patients with acute respiratory failure. An increase in partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) has been described after 4 hours in prone position in adult patients with severe acute respiratory failure. Similarly, a decrease of the oxygenation index has been found after 8 hours of prone positioning in adult patients with respiratory failure from coronavirus disease of 2019 (COVID-19) associated acute respiratory distress syndrome. The process of prone positioning appeared safe also in critically ill infants and children. In a randomized control trial, it has been shown that in 90% of prone positioning oxygenation index decreased of more than 10% in children with acute lung injury.

Electrical impedance tomography (EIT) and lung ultrasound (LUS) are two non-invasive methods to monitor aeration and lung function parameters. EIT can quantify regional distribution of ventilation as well as improvement in end-expiratory air content. EIT has been used at bedside in critically ill adult patients to measure effects of prone position and also in infants with respiratory distress syndrome. On the other side, LUS has become an increasingly popular diagnostic bedside tool for lung examination. It is considered reliable and fast to detect various lung-related pathologies, such as pneumonia, atelectasis, pneumothorax, and interstitial syndrome.

The main objective is to determine the short-term effect of prone positioning in infants with infection-associated severe acute respiratory distress syndrome. To accomplish this, oxygenation parameters and measurements from EIT and LUS will be compared in mechanically ventilated infants in prone position versus supine position after surfactant administration.

Study Type

Interventional

Enrollment (Estimated)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients hospitalized at Pediatric Intensive Care Unit (PICU) or Neonatal Intensive Care Unit (NICU) of the Medical University Vienna.
  • Patients aged >36 weeks (corrected gestational age) and <24 months.
  • Patient intubated and mechanically ventilated for at least 6 hours, with an expected requirement of invasive ventilatory support for at least 12 hours.
  • Clinical picture strongly suggestive for acute bronchiolitis or pneumonia (fever, fine crackles, prolonged expiration, lung hyperinflation and/or findings of new infiltrates consistent with acute pulmonary parenchymal disease on chest X-ray).
  • Severe pediatric acute respiratory distress syndrome (ARDS), defined by OSI ≥12.3 (wean FIO2 to maintain SpO2 ≤ 97% to calculate oxygen saturation index).
  • Written informed consent obtained from parents.

Exclusion Criteria:

  • Clinical context

    • Need for O2 supplementation to maintain SpO2>94% in the 4 weeks preceding hospitalization in the PICU/NICU
    • Cyanotic congenital heart disease Cardiogenic pulmonary edema
    • Severe pulmonary hypertension
    • Untreated pneumothorax
    • Severe neurological abnormalities
    • Other severe congenital anomalies such as congenital diaphragmatic hernia
    • Ongoing cardiopulmonary resuscitation or limitation of life support

  • Contradictions for prone positioning (adapted from Guerin, C., et al., Prone positioning in severe acute respiratory distress syndrome. N Engl J Med, 2013. 368(23): p. 2159-68):

    • Intracranial pressure >30 millimeters of mercury (mmHg) in supine position or cerebral perfusion pressure <60 mmHg
    • Massive hemoptysis requiring an immediate surgical or interventional radiology procedure
    • Tracheal surgery or sternotomy during the previous 15 days
    • Serious facial trauma or facial surgery during the previous 15 days
    • Deep venous thrombosis treated for less than 2 days
    • Cardiac pacemaker inserted in the last 2 days
    • Unstable spine, femur, or pelvic fractures
    • Use of extracorporeal membrane oxygenation (ECMO) before inclusion
    • Lung transplantation
    • Burns on more than 20% of the body surface

  • Other non-inclusion criteria

    • Indication not to attempt resuscitation
    • Patient already recruited for other clinical studies
    • Patients who already received surfactant in the last 4 weeks
    • Thoracic skin lesions or wounds on the thorax, where the EIT-electrode-belt would be placed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prone Group
Turn patient in prone position after surfactant administration. After 6 hours turn patient in supine position and perform EIT and LUS.
Other: Prone positioning
Turn patient in prone position after surfactant administration.
No Intervention: Supine Group
Leave patient in supine position after surfactant administration. After 6 hours perform EIT and LUS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Oxygenation saturation index
Time Frame: Change from baseline oxygenation saturation index at 6 hours

Oxygenation saturation index (OSI) defined by [FiO2 x mean airway pressure x 100]/Peripheral oxygen saturation (SpO2) in millibar [mbar] (wean FiO2 to maintain SpO2 ≤ 97% to calculate OSI).

OSI values will be calculated after a stable value of SpO2 and mean airway pressure (MAP) will be reached (see ventilation management). The OSI gradient will be calculated as follows: 100*((OSI (0) - OSI (6h)) / OSI (0) = change of OSI in %. OSI (0) accounts for the OSI prior to the prone position (intervention) and OSI (6h) accounts for the OSI six hours after the intervention.
Change from baseline oxygenation saturation index at 6 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chang in Lung Ultrasound
Time Frame: Change from baseline LUS score at 6 hours
Each lung (left and right) is divided into 6 areas (upper anterior, lower anterior, upper lateral, lower lateral, upper posterior, lower posterior). The Lung Ultrasound Score is assigned as follows: 0 indicates A-pattern (defined by the presence of the only A-lines); 1, B-pattern (defined as the presence of ≥3 well-spaced B-lines); 2, severe B pattern (defined as the presence of crowded and coalescent B-lines with or without consolidations limited to the subpleural space); and 3, extended consolidations. The total LUS score ranges from 0 (best) to 36.
Change from baseline LUS score at 6 hours
Change in the Distribution of the End-Expiratory Lung Volume
Time Frame: Change from baseline EELV at 6 hours
End-expiratory lung impedance (EELV) is the average of the measured impedance at the end of expiration [arbitrary units].
Change from baseline EELV at 6 hours
Change in the Distribution of the Tidal Volume
Time Frame: Change from baseline tidal volume at 6 hours
Tidal volume is the average difference of end-inspiratory and end-expiratory impedance measurements [arbitrary units].
Change from baseline tidal volume at 6 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Tobias Werther, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2022

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

July 29, 2021

First Submitted That Met QC Criteria

August 4, 2021

First Posted (Actual)

August 12, 2021

Study Record Updates

Last Update Posted (Actual)

November 20, 2024

Last Update Submitted That Met QC Criteria

November 18, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1426/2021

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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