Clinical trial NCT04000568: Breathing Variability and NAVA in Neonates
Official 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neonatal Respiratory Distress Syndrome
Prematurity
Keywords: Preterm Infant
Respiratory Distress Syndrome
Non-invasive respiratory Support
Neurally Adjust Respiratory Assist (NAVA)
Nasal Intermittent Positive Pressure Ventilation
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: Politecnico di Milano
First posted: 2019-06-27
Enrollment: 25
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: preterm infants born \< 37 weeks of gestation, requiring non-invasive respiratory support

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in breath-by-breath variability of tidal breathing amplitude
timeFrame: over the last 30 minutes of each step (crossover trial, 2 steps, 1 hour-step)
Secondary outcomes:
measure: Respiratory Rate
timeFrame: 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
measure: Inspiratory Time
timeFrame: 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
measure: Duty Cycle
timeFrame: 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
measure: Total Respiratory System Oscillatory Resistance
timeFrame: at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)
measure: Total Respiratory System Oscillatory Reactance
timeFrame: at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)
measure: SpO2/FiO2 (Fraction on inspired oxygen)
timeFrame: 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
measure: tpCO2, Transcutaneous Carbon Dioxide Partial Pressure (mmHg)
timeFrame: 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
measure: Rate of apneas, desaturations, bradycardias
timeFrame: over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)
measure: Rate of patient-ventilator asynchronies
timeFrame: over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)
Other outcomes:
measure: Patient's comfort: COMFORT-B scale
timeFrame: at the end of each 1-hour step
measure: Number of caregivers interventions required
timeFrame: at the end of each 1-hour step
Locations:
city: Milan
country: Italy
facility: NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
state: MI
Study officials:
affiliation: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
name: Anna Lavizzari, MD
role: PRINCIPAL_INVESTIGATOR
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