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Completed

NCT Number: NCT04000568

Breathing Variability and NAVA in Neonates

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.

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Key information

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Respiratory support: NAVA -NIV and PC-NIV

Other

The infants enrolled will receive respiratory assistance by NAVA-NIV and PC-NIV in a randomized order

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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).

  5. 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).

  6. 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.

  7. 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

  8. 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

  9. 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

Other outcomes

  1. 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.

  2. 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 ...

Sponsors and collaborators

Lead sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Other

Collaborators

  • Politecnico di Milano

Registry information

Official study title

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

Acronym: BRAVe NANO

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Jun 27, 2019
Registry last updated
Mar 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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