Prediction of Extubation Readiness in Extreme Preterm Infants by the Automated Analysis of CardioRespiratory Behavior

March 28, 2019 updated by: Guilherme Sant'Anna, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Prediction of Extubation Readiness in Extreme Preterm Infants by the Automated Analysis of CardioRespiratory Behavior: the APEX Study

The investigators hypothesize that machine learning methods using a combination of novel, quantitative measures of cardio-respiratory variability can accurately predict the optimal time to extubate extreme preterm infants. In this multicenter prospective study, cardiorespiratory signals will be recorded from 250 extreme preterm infants who are eligible for extubation. Automated signal analysis algorithms will compute a variety of metrics for each infant describing the cardiorespiratory state. Machine learning methods will then be used to find the optimal combination of these statistical measures and clinical features that provide the best overall predictor of extubation readiness. Finally, investigators will develop an Automated system for Prediction of EXtubation (APEX) that will integrate the software for data acquisition, signal analysis, and outcome prediction into a single application suitable for use by medical personnel in the Neonatal Intensive Care Unit (NICU). The performance of APEX will later be clinically validated in 50 additional infants prospectively.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

At birth, extreme preterm infants (≤28 weeks) have inconsistent respiratory drive, airway instability, surfactant deficiency and immature lungs that frequently result in respiratory failure. Management of these infants is difficult and most will require endotracheal intubation and mechanical ventilation (ETT-MV) within the first days of life to survive. ETT-MV is an invasive therapy that is associated with adverse clinical outcomes including ventilator-associated pneumonia, impaired neurodevelopment, and increased mortality. Consequently, clinicians try to remove ETT-MV as quickly as possible. However, 25 to 35% of these extubation attempts will fail and infants will require reintubation, an intervention that is also associated with increased morbidity and mortality. Therefore physicians must determine the optimal time for extubation which minimizes the duration of ETT-MV and maximizes the chances of success. A variety of objective measures have been proposed to assist with this decision but none has proven to be useful clinically. Investigators from this group have recently explored the predictive power of indices of autonomic nervous system function based on measurements of heart rate (HRV) and respiratory variability (RV). The use of sophisticated, automated algorithms to analyze those cardiorespiratory signals have shown some promising preliminary results in predicting which infants can be extubated successfully.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
266

Contacts and Locations

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

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital
      • Montreal, Quebec, Canada, H3A 1A1
        • Royal Victoria Hospital
  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Women and Infants Hospital of Rhode Island

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Extreme preterm infants who are requiring endotracheal tube mechanical ventilation (ETT-MV).

Description

Inclusion Criteria:

  • All infants admitted to the NICU with a birth weight ≤ 1250 grams AND
  • Need for endotracheal tube mechanical ventilation

Exclusion Criteria:

  • Infants with major congenital anomalies
  • Infants with congenital heart disease and cardiac arrhythmias
  • Infants receiving vasopressor or sedative drugs at the time of extubation
  • Infants extubated directly from high frequency ventilation
  • Infants extubated to room air, oxyhood or low-flow nasal cannula

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Intubated extreme preterm infants
Infants with a birth weight ≤ 1250 grams and requiring endotracheal tube and mechanical ventilation
Other: Cardiorespiratory signal acquisition

Cardiorespiratory signals will measure heart rate (using electrocardiography), chest and abdominal movements (using respiratory inductance plethysmography) and oxygen saturation (using pulse oximetry). Data will be acquired during 2 recording periods:

  1. A 60-minute period while the infant receives any mode of conventional mechanical ventilation
  2. A 5-minute period prior to extubation while the mode of ventilation is switched to endotracheal tube CPAP (Continuous Positive Airway Pressure), so that the respiratory pattern will be controlled by the infant

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Extubation Failure
Time Frame: Within 72 hours of extubation

Infants will be considered to have failed extubation if they meet one or more of the following criteria within 72 hours of extubation:

  1. Fraction of inspired oxygen (FiO2) > 0.5 in order to maintain oxygen saturation (SpO2) > 88% or PaO2 > 45 mmHg (for 2 consecutive hours)
  2. PaCO2 > 55-60 mmHg with a pH < 7.25 in two consecutive blood gases done 1-2 hours apart
  3. 1 episode of apnea requiring positive pressure ventilation with bag and mask
  4. Multiple episodes of apnea (≥ 6 episodes / 6 hours).
Within 72 hours of extubation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The need for reintubation within 72h of the first planned extubation
Time Frame: Within 72 hours of extubation
The decision to re-intubate will be made by the responsible physician, who may not always follow the guidelines stated in the primary objective. Therefore, reintubation will be assessed as a secondary outcome.
Within 72 hours of extubation
The need for reintubation
Time Frame: Anytime from the first planned extubation until discharge from the neonatal intensive care unit
Infants will be prospectively followed from birth until discharge from the NICU. Therefore, infants who require reintubation at any time point from the first planned extubation until discharge from the neonatal intensive care unit will be documented
Anytime from the first planned extubation until discharge from the neonatal intensive care unit

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Total duration of ETT-MV
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Total duration (in days) of endotracheal tube mechanical ventilation from the time of birth until discharge from the hospital
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Intraventricular hemorrhage
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Presence of Intraventricular Hemorrhage (IVH) from time of birth until discharge from the hospital. If IVH is present, the grade of the hemorrhage will be specified (as per Volpe's classification)
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Patent Ductus Arteriosus
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Presence of a Patent Ductus Arteriosus (PDA) from the time of birth until discharge from hospital. If present, the therapeutic measures taken for closing the PDA (medical or surgical) will also be specified.
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Oxygen supplementation at 28 days of life
Time Frame: This outcome will be assessed when participants have 28 days of life
The need for any oxygen supplementation at 28 days of life
This outcome will be assessed when participants have 28 days of life
Bronchopulmonary Dysplasia
Time Frame: This outcome will be assessed when participants are 36 weeks post-conceptual age

The presence of Bronchopulmonary Dysplasia (BPD) will be assessed at 36 weeks Post Conceptual Age (PCA) and classified as mild, moderate or severe.

  • Mild BPD: oxygen supplementation at 28 days of life but none at 36 weeks PCA
  • Moderate BPD: FiO2 requirements of less than 0.3 at 36 weeks PCA
  • Severe BPD: FiO2 requirements over 0.3 or CPAP or mechanical ventilation at 36 weeks PCA
This outcome will be assessed when participants are 36 weeks post-conceptual age
Retinopathy of Prematurity
Time Frame: This outcome will be assessed at the time of the first eye exam (approximately 31 weeks PCA) until the final eye exam prior to hospital discharge
Participants will be assessed for the presence or absence of Retinopathy of Prematurity (ROP)
This outcome will be assessed at the time of the first eye exam (approximately 31 weeks PCA) until the final eye exam prior to hospital discharge
Necrotizing Enterocolitis
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Participants will be assessed for the presence or absence of Necrotizing Enterocolitis (NEC) throughout the course of their hospitalization. NEC will be classified according to Bell's modified staging criteria.
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Death
Time Frame: Participants will be followed for the duration of hospital stay in the NICU, an expected average of 10 weeks
Death occuring anytime during the hospitalization course in the NICU.
Participants will be followed for the duration of hospital stay in the NICU, an expected average of 10 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Canadian Institutes of Health Research (CIHR)
Wayne State University
Brown University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Guilherme M Sant'Anna, MD, McGill University
  • Principal Investigator: Guilherme M Sant'Anna, MD, McGill University
  • Principal Investigator: Robert E Kearney, PhD, McGill University
  • Principal Investigator: Wissam Shalish, MD, McGill University
  • Principal Investigator: Karen A Brown, MD, McGill University
  • Principal Investigator: Doina Precup, McGill University
  • Principal Investigator: Sanjay Chawla, MD, Wayne State University
  • Principal Investigator: Martin Keszler, MD, Brown University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APEX 01
  • 288299 (Other Grant/Funding Number: CIHR)
  • 12-387-PED (Other Identifier: MUHC)

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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