Breathing Variability and NAVA in Neonates (BRAVe NANO)

March 10, 2023 updated by: Anna Lavizzari, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Breathing Pattern Variability in Preterm Infants: Effect of Non-invasive Neurally Adjusted Ventilatory Assist (NAVA-NIV) Versus Nasal Intermittent Positive Pressure Ventilation (PC-NIV), a Crossover Study

The current study is a crossover trial, aiming at evaluating the effect of NAVA -NIV compared to Nasal Intermittent Positive Pressure Ventilation (PC-NIV) at the same level of peak inspiratory pressure, in terms of: breath-by-breath variability of tidal breathing amplitude, variability of the other breathing patterns; lung mechanics; gas exchange; rate of episodes of apnea; bradycardia and desaturations; respiratory asynchrony and comfort, in preterm infants < 37+0 weeks+days post-menstrual age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Preterm infants matching the inclusion criteria (listed elsewhere) will be enrolled in a cross- over trial of two modes of non-invasive respiratory support: nasal intermittent positive pressure ventilation (PC-NIV) and NAVA NIV (Sevo-n Neonatal Ventilator, GETINGE, Solna, Sweden). Parental consent will be collected prior to the study. A 20-minute registration of ventilator parameters during assistance on NAVA-NIV will allow calculating the mean PIP (peak inspiratory pressure), in order to compare the two modes at the same level of PIP. The ventilator settings other than PIP (i.e. FiO2 (fraction of inspired oxygen), PEEP (positive end-expiratory pressure), IT (inspiratory time), RR (respiratory rate), NAVA level) will be based on the setting optimized by the attending physicians prior to the study entry. FiO2 will be adjusted in order to maintain SpO2 88-93% in infants ≤ 32 weeks of postconceptional age, 90-95% in infants > 32 weeks of postconceptional age. Infants will then receive a randomized sequence of 1-hour assistance by NAVA NIV and 1-hour assistance PC-NIV or vice-versa. Infants will receive respiratory support in a standardized supine position during the study period.

Two, high-resolution, small cameras will be placed in the infant's incubator to detect chest and abdominal movements, by means of two markers placed on the infant's chest and abdomen. Ventilators parameters (flow, pressure, volume, the electrical activity of the diaphragm), vital signs (SpO2, HR (heart rate), ABP( arterial blood pressure)), transcutaneous gases, changes in end-expiratory lung volume will be collected continuously. Episodes of apnea, bradycardia or desaturations and the number of interventions required by the nurses and the attending physicians during the study (e.g. adjustment of the interface, suctioning, interventions to provide comfort or optimize the respiratory support...) will be also collected during the study. Patients' comfort will be assessed at the end of each sequence by the attending nurse by means of the COMFORT scale. Lung mechanics will be measured at the end of each sequence by means of the Forced Oscillation Technique.

Data will be then analysed and compared offline.

Study Type

Observational

Enrollment (Actual)

25

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

  • Italy
    • MI
      • Milan, MI, Italy, 20122
        • NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

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

1 day to 3 months (Child)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

preterm infants born < 37 weeks of gestation, requiring non-invasive respiratory support

Description

Inclusion Criteria:

  • preterm birth < 37 weeks of gestational age
  • need of non-invasive respiratory support
  • parental consent

Exclusion Criteria:

  • Major congenital abnormalities of the cardio-respiratory systems
  • Severe Respiratory Failure requiring intubation and mechanical ventilation at the time of the study; pH < 7.25 pCO2> 65 mmHg; pulmonary hypertension of the newborn requiring pharmacological treatment (Nitric Oxide, Sildenafil)
  • Hypoxic-Ischaemic Encephalopathy, neurological disorders which may compromise the integrity of the neural transmission from the brain to the diaphragm
  • Contraindication to orogastric tube insertion (e.g. oesophageal atresia, gastric perforation...)
  • Haemodynamic instability requiring inotropic agents
  • Any condition that would expose the patient to undue risk as deemed by the attending physician

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

  • Observational Models: Case-Crossover
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Study Population
All the infants enrolled in the study will receive 1 h of NAVA-NIV and 1h PC-NIV in a cross-over study design
Other: Respiratory support: NAVA -NIV and PC-NIV
The infants enrolled will receive respiratory assistance by NAVA-NIV and PC-NIV in a randomized order

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in breath-by-breath variability of tidal breathing amplitude
Time Frame: over the last 30 minutes of each step (crossover trial, 2 steps, 1 hour-step)
Tidal breathing amplitude will be recorded continuously by mean of two, high-resolution cameras placed inside the infant's incubator and skin (non-invasive) markers. Data will be analysed a posteriori applying the DFA (Detrended Fluctuation Analysis) technique.
over the last 30 minutes of each step (crossover trial, 2 steps, 1 hour-step)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Respiratory Rate
Time Frame: at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Respiratory rate (breaths/min) will be recorded from the ventilator
at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Inspiratory Time
Time Frame: at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Inspiratory time (msec) will be recorded from the ventilator tracing
at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Duty Cycle
Time Frame: at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Duty Cycle (Inspiratory Time/ Total Time), will be calculated from the ventilator tracing
at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Total Respiratory System Oscillatory Resistance
Time Frame: at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)
Total Respiratory System Oscillatory Resistance will be measured by the Forced Oscillation Technique (FOT) at the end of each step, by superimposing to the ventilator waveform an oscillatory pressure of small amplitude at 10 Hz (Fabian, ACUTRONIC Medical Systems AG, Switzerland).
at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)
Total Respiratory System Oscillatory Reactance
Time Frame: at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)
Total Respiratory System Oscillatory Reactance will be measured by the Forced Oscillation Technique (FOT) at the end of each step, by superimposing to the ventilator waveform an oscillatory pressure of small amplitude at 10 Hz (Fabian, ACUTRONIC Medical Systems AG, Switzerland).
at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)
SpO2/FiO2 (Fraction on inspired oxygen)
Time Frame: at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
SpO2 and FiO2 will be monitored continuously and FiO2 will be adjusted to the target SpO2 88-93% in infants ≤ 32 weeks of postconceptional age, SpO2 90-95% in infants > 32 weeks of postconceptional age.
at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
tpCO2, Transcutaneous Carbon Dioxide Partial Pressure (mmHg)
Time Frame: at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
tpCO2 will be monitrored continuously over the study period and recorded at specific time points
at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step
Rate of apneas, desaturations, bradycardias
Time Frame: over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)
Episodes of apnoeas, desaturations, bradycardias will be recorded over each study period
over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)
Rate of patient-ventilator asynchronies
Time Frame: over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)
Patient-ventilator asynchronies will be calculated by continuous recording of ventilator parameters (flow, pressure, volume and electrical diaphragmatic activity) and by continuous recording of abdominal and chest movements by high resolution cameras placed in the incubators and skin markers on abdomen and chest
over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient's comfort: COMFORT-B scale
Time Frame: at the end of each 1-hour step
Patient's comfort will be assessed by the attending nurse at the end of each step by means of the COMFORT-B scale (COMFORT behavioural scale). The COMFORT-B scale is a validated tool for assessing patients' comfort in Pediatric Intensive Care Unit.It includes the following items for comfort evaluation: alertness, calmness, respiratory response, cry, physical movements, muscle tone, facial tension. For each item a descriptive scale form 1 (the best) to 5 (the worst) is indicated and the operator can choose what is the most appropriate for the patient.
at the end of each 1-hour step
Number of caregivers interventions required
Time Frame: at the end of each 1-hour step
The number of interventions required to the attending personnel during each step will be also recorded: for instance interventions to improve comfort, to adjust the ventilator interface, to optimize the efficacy of respiratory support, suctioning ...
at the end of each 1-hour step

Collaborators and Investigators

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

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Collaborators

Politecnico di Milano

Investigators

  • Principal Investigator: Anna Lavizzari, MD, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico

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)

May 2, 2019

Primary Completion (Actual)

September 30, 2022

Study Completion (Actual)

November 30, 2022

Study Registration Dates

First Submitted

May 31, 2019

First Submitted That Met QC Criteria

June 26, 2019

First Posted (Actual)

June 27, 2019

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 10, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRAVe NANO (NIV)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

the study protocol, statistical analysis plan an Informed Consent (only in the original language, available in English under request) will be available from the study protocol submission date. Analytic code status: still undecided.

IPD Sharing Time Frame

at protocol submission

IPD Sharing Access Criteria

free

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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