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

Prediction of Extubation Readiness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01909947
• Other study ID #: APEX 01
• Secondary ID: 28829912-387-PED
• Status: Completed
• Start date: September 2013
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: McGill University Health Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: December 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Prediction of Extubation Readiness

Intervention

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: A 60-minute period while the infant receives any mode of conventional mechanical ventilation 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

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
United States	Wayne State University	Detroit	Michigan
United States	Women and Infants Hospital of Rhode Island	Providence	Rhode Island

Sponsors (4)

Lead Sponsor	Collaborator
McGill University Health Center	Brown University, Canadian Institutes of Health Research (CIHR), Wayne State University

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total duration of ETT-MV	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
Other	Intraventricular hemorrhage	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
Other	Patent Ductus Arteriosus	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
Other	Oxygen supplementation at 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
Other	Bronchopulmonary Dysplasia	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
Other	Retinopathy of Prematurity	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
Other	Necrotizing Enterocolitis	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
Other	Death	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
Primary	Extubation Failure	Infants will be considered to have failed extubation if they meet one or more of the following criteria within 72 hours of extubation: Fraction of inspired oxygen (FiO2) > 0.5 in order to maintain oxygen saturation (SpO2) > 88% or PaO2 > 45 mmHg (for 2 consecutive hours); PaCO2 > 55-60 mmHg with a pH < 7.25 in two consecutive blood gases done 1-2 hours apart; 1 episode of apnea requiring positive pressure ventilation with bag and mask; Multiple episodes of apnea (= 6 episodes / 6 hours).	Within 72 hours of extubation
Secondary	The need for reintubation within 72h of the first planned 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
Secondary	The need for reintubation	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