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Neonatal Respiratory Distress SyndromeBRAVe NANONCT04000568

Breathing Variability and NAVA in Neonates

An observational study of Neonatal Respiratory Distress Syndrome and Prematurity, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 1 day to 3 months
What is being tested?
Respiratory support: NAVA -NIV and PC-NIV
How many people
25 participants
Where
1 siteItaly
Study dates
2 May 2019to 30 Nov 2022
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 day to 3 months
  • All sexes
  • Child

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

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

    Milan, MI, 20122

Other trials in Italy

About this study

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

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.

Read the 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.

Being tested
Respiratory support: NAVA -NIV and PC-NIV
Keywords
Preterm Infant, Respiratory Distress Syndrome, Non-invasive respiratory Support, Neurally Adjust Respiratory Assist (NAVA), Nasal Intermittent Positive Pressure Ventilation
Medical subject headings
Respiratory Distress Syndrome, Newborn, Premature Birth, Respiratory Distress Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Respiratory support: NAVA -NIV and PC-NIVOther

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

Study groups in NCT04000568
Study groupRoleWhat they receive
Study PopulationAll the infants enrolled in the study will receive 1 h of NAVA-NIV and 1h PC-NIV in a cross-over study design
Receives: Other: Respiratory support: NAVA -NIV and PC-NIV

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in breath-by-breath variability of tidal breathing amplitude

    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.

    Measured: over the last 30 minutes of each step (crossover trial, 2 steps, 1 hour-step)

Secondary outcomes (9)

  1. Respiratory Rate

    Respiratory rate (breaths/min) will be recorded from the ventilator

    Measured: 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

  2. Inspiratory Time

    Inspiratory time (msec) will be recorded from the ventilator tracing

    Measured: 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

  3. Duty Cycle

    Duty Cycle (Inspiratory Time/ Total Time), will be calculated from the ventilator tracing

    Measured: 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

  4. Total Respiratory System Oscillatory Resistance

    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).

    Measured: at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)

  5. Total Respiratory System Oscillatory Reactance

    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).

    Measured: at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step)

  6. SpO2/FiO2 (Fraction on inspired oxygen)

    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.

    Measured: 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

  7. tpCO2, Transcutaneous Carbon Dioxide Partial Pressure (mmHg)

    tpCO2 will be monitrored continuously over the study period and recorded at specific time points

    Measured: 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

  8. Rate of apneas, desaturations, bradycardias

    Episodes of apnoeas, desaturations, bradycardias will be recorded over each study period

    Measured: over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)

  9. Rate of patient-ventilator asynchronies

    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

    Measured: over 1 hour, for each step (in a 2-step crossover trial, 1-hour step)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2019
  2. Study start2 May 2019
  3. Primary completion30 Sep 2022
  4. Study completion30 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case crossover
Time perspective
Prospective
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04000568
Sponsor's protocol ID
BRAVe NANO (NIV)
Acronym
BRAVe NANO
Status last verified
Mar 2023
First submitted
31 May 2019
Last updated
14 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics. 2000 Oct;106(4):659-71. doi: 10.1542/peds.106.4.659.

    PubMed 11015506

  • Ancel PY, Goffinet F; EPIPAGE-2 Writing Group; Kuhn P, Langer B, Matis J, Hernandorena X, Chabanier P, Joly-Pedespan L, Lecomte B, Vendittelli F, Dreyfus M, Guillois B, Burguet A, Sagot P, Sizun J, Beuchee A, Rouget F, Favreau A, Saliba E, Bednarek N, Morville P, Thiriez G, Marpeau L, Marret S, Kayem G, Durrmeyer X, Granier M, Baud O, Jarreau PH, Mitanchez D, Boileau P, Boulot P, Cambonie G, Daude H, Bedu A, Mons F, Fresson J, Vieux R, Alberge C, Arnaud C, Vayssiere C, Truffert P, Pierrat V, Subtil D, D'Ercole C, Gire C, Simeoni U, Bongain A, Sentilhes L, Roze JC, Gondry J, Leke A, Deiber M, Claris O, Picaud JC, Ego A, Debillon T, Poulichet A, Coline E, Favre A, Flechelles O, Samperiz S, Ramful D, Branger B, Benhammou V, Foix-L'Helias L, Marchand-Martin L, Kaminski M. Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study. JAMA Pediatr. 2015 Mar;169(3):230-8. doi: 10.1001/jamapediatrics.2014.3351.

    PubMed 25621457

  • Hennessy EM, Bracewell MA, Wood N, Wolke D, Costeloe K, Gibson A, Marlow N; EPICure Study Group. Respiratory health in pre-school and school age children following extremely preterm birth. Arch Dis Child. 2008 Dec;93(12):1037-43. doi: 10.1136/adc.2008.140830. Epub 2008 Jun 18.

    PubMed 18562451

  • Doyle LW, Carse E, Adams AM, Ranganathan S, Opie G, Cheong JLY; Victorian Infant Collaborative Study Group. Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years. N Engl J Med. 2017 Jul 27;377(4):329-337. doi: 10.1056/NEJMoa1700827.

    PubMed 28745986

  • Dumpa V, Bhandari V. Surfactant, steroids and non-invasive ventilation in the prevention of BPD. Semin Perinatol. 2018 Nov;42(7):444-452. doi: 10.1053/j.semperi.2018.09.006. Epub 2018 Oct 2.

    PubMed 30343941

  • Bhandari V. The potential of non-invasive ventilation to decrease BPD. Semin Perinatol. 2013 Apr;37(2):108-14. doi: 10.1053/j.semperi.2013.01.007.

    PubMed 23582965

  • Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008 Feb 14;358(7):700-8. doi: 10.1056/NEJMoa072788.

    PubMed 18272893

  • SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sanchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16.

    PubMed 20472939

  • Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L370-5. doi: 10.1152/ajplung.00036.2003.

    PubMed 12851212

  • Arold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med. 2002 Feb 1;165(3):366-71. doi: 10.1164/ajrccm.165.3.2010155.

    PubMed 11818322

  • Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, Suki B. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006 Feb;34(2):439-45. doi: 10.1097/01.ccm.0000196208.01682.87.

    PubMed 16424726

  • Thammanomai A, Hueser LE, Majumdar A, Bartolak-Suki E, Suki B. Design of a new variable-ventilation method optimized for lung recruitment in mice. J Appl Physiol (1985). 2008 May;104(5):1329-40. doi: 10.1152/japplphysiol.01002.2007. Epub 2008 Mar 13.

    PubMed 18339891

  • Berry CA, Suki B, Polglase GR, Pillow JJ. Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome. Pediatr Res. 2012 Oct;72(4):384-92. doi: 10.1038/pr.2012.97. Epub 2012 Jul 17.

    PubMed 22805999

  • Bartolak-Suki E, Noble PB, Bou Jawde S, Pillow JJ, Suki B. Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs. Front Physiol. 2017 Jun 23;8:425. doi: 10.3389/fphys.2017.00425. eCollection 2017.

    PubMed 28690548

  • Arold SP, Malavia N, George SC. Mechanical compression attenuates normal human bronchial epithelial wound healing. Respir Res. 2009 Feb 12;10(1):9. doi: 10.1186/1465-9921-10-5.

    PubMed 19171062

Questions about this trial

What is this clinical trial studying?

An observational study of Neonatal Respiratory Distress Syndrome and Prematurity, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04000568, which also lists 28 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2023.

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