Premature BirthEASYNNEONCT04068558
sNIPPV Versus NIV-NAVA in Extremely Premature Infants
A study testing VNI-NAVA/sNIPPV and sNIPPV/VNI-NAVA in people with Premature Birth and Ventilator Lung; Newborn, run by Centre Hospitalier Intercommunal Creteil at 1 site in France.
Trial summary
The aim of this study is to demonstrate a significant decrease in asynchrony with NIV-NAVA using the Servo n ventilator (Getinge, Sweden), as compared to abdominal triggered (Graseby capsule) synchronized nasal intermittent positive pressure ventilation (sNIPPV) using the Infant Flow CPAP device (Care Fusion, USA). Read more about this study
- Who is it for?
- Ages 3 days and older
- Conditions the study is for
- Premature Birth, Ventilator Lung; Newborn
- What is being tested?
- VNI-NAVA/sNIPPV and sNIPPV/VNI-NAVA
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- 9 Dec 2019to 11 Mar 2021
- Phase
- Interventional
- 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 3 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Premature infants born before 28 weeks of gestation
- Corrected age below 32 weeks of gestation
- Postnatal age > or = 3 days
- Receiving NIPPV (any mode)
- Equipped with an Edi catheter
- Receiving caffein treatment
Show all 16Show fewer
- Parental consent
- Recipient of French social security coverage
- Non-inclusion criteria:
- More than 1 apnea/hour requiring bag-mask ventilation, or pH<7.2 and/or TcPCO2>70, or FiO2>0.6 in the previous 6 hours.
- Nasal trauma precluding the use of non-invasive ventilation
- Major congenital anomalies
- Grade III or higher intraventricular hemorrhage
- Use of anesthetics or sedative within the past 24 hours, except opioids for iatrogenic withdrawal treatment
- Hemodynamic compromise defined as a mean blood pressure less than gestational age (in mmHg) or a capillary refill time more than 3 seconds
- Neuro-muscular disorders
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Synchronized Nasal Intermittent Positive Pressure Ventilation Versus Noninvasive Neurally Adjusted Ventilatory Assist Ventilation in Extremely Premature Infants: a Randomized Crossover Trial
The aim of this study is to demonstrate a significant decrease in asynchrony with NIV-NAVA using the Servo n ventilator (Getinge, Sweden), as compared to abdominal triggered (Graseby capsule) synchronized nasal intermittent positive pressure ventilation (sNIPPV) using the Infant Flow CPAP device (Care Fusion, USA).
All of the data obtained can be used to develop a large-scale study aimed at reducing the rate of re-intubation in the study population (pilot study). In fact, the re-intubation criteria for extremely premature children are based on clinical criteria (desaturations, apnea, signs of respiratory control) and paraclinical criteria (FiO2, Potential hydrogen (pH), PCO2).
The results of this pilot study will help to develop an adapted methodology and to calculate a sample size to compare the 2 modes of NIV to the test on a clinical criterion: the rate of re-intubation after extubation, which is classically high in these patients.
Read the detailed description
The use of non-invasive ventilation has significantly reduced morbidity and mortality in premature newborns by reducing the pulmonary lesions caused by invasive ventilation. Currently, variable flow continuous positive airway pressure (CPAP) devices, such as the infant flow® driver, are considered more efficient than constant flow pressure sources. Nasal intermittent positive pressure ventilation, as compared to CPAP, might reduce the extubation failure rate, but has no impact on mortality or bronchopulmonary dysplasia. However, data is lacking on the interest of synchronization and on the effect of the different available interfaces (prongs, masks, cannulas). In addition, the ventilatory characteristics (high respiratory rate and low inspiratory effort) of the premature infant increase the risk of asynchrony between the patient and the ventilator, which is a major cause of poor tolerance for this type of ventilation.
NAVA (neurally adjusted ventilatory assist) is a recent ventilatory mode that offers proportional assistance to respiratory work based on the measured electrical activity of the diaphragm via oesophageal electrodes. It thus allows a regulation of inspiratory pressures and time by the patient him/herself. The physiological effects of NAVA have been primarily described in intubated neonates and studies have shown a significantly improved synchronization and significantly decreased inspiratory pressures in patients ventilated with NAVA compared to intermittent controlled ventilatory support. However, the currently available evidence is limited and no beneficial effect on morbidity or mortality has been identified so far .
There are few studies on noninvasive NAVA (NIV-NAVA) conducted exclusively in neonates, most of which included a limited number of patients. Only one study to date compared NIV-NAVA to another synchronized NIV mode (NIV pressure support) using the Servo-i ventilator. This prospective crossover study found a significant decrease in peak inspiratory pressure (PIP), FiO2, frequency and length of desaturations in the NIV-NAVA group.
Decreased asynchrony has been observed during NIV-NAVA as compared to pressure-support NIV In adult patients and in 6 children hospitalized in the Pediatric ICU (median age 18 months).
In premature neonates, variable flow CPAP is preferentially used. Synchronized intermittent positive pressure can be delivered using a variable flow device and a Graseby abdominal capsule. Since variable flow CPAP is considered the most efficient pressure generator, it is legitimate to compare synchronization performance of the variable flow synchronized nasal intermittent positive pressure ventilation (sNIPPV) to NIV-NAVA. This comparison has never been performed so far, to our knowledge.
We hypothesize that synchronization will be markedly improved with NIV-NAVA as compared to sNIPPV.
- Conditions
- Premature Birth, Ventilator Lung; Newborn
- Being tested
- VNI-NAVA/sNIPPV, sNIPPV/VNI-NAVA
- Keywords
- neurally adjusted ventilatory assist, synchronized nasal intermittent positive pressure ventilation
- Medical subject headings
- Premature Birth, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VNI-NAVA/sNIPPVDevice
Ventilation of the child in NIV-NAVA for 2 hours then ventilation of the child in sNIPPV for two hours. The ventilation periods consist of one hour of wash-out and one hour of data collection
sNIPPV/VNI-NAVADevice
Ventilation of the child in sNIPPV for 2 hours then ventilation of the child in NIV-NAVA for two hours. The ventilation periods consist of one hour of wash-out and one hour of data collection
| Study group | Role | What they receive |
|---|---|---|
| VNI-NAVA/sNIPPV | Experimental | Ventilation of the child non-invasive ventilation (VNI) NAVA then sNIPPV Receives: Device: VNI-NAVA/sNIPPV |
| sNIPPV/VNI-NAVA | Experimental | Ventilation of the child sNIPPV then non-invasive ventilation (VNI) NAVA Receives: Device: sNIPPV/VNI-NAVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Asynchrony index
Asynchrony index as previously defined in the literature using the following parameters: Ineffective effort (IE): presence of an inspiratory electromyographic signal not followed by pressurization; Late cycling (LC): a cycle with an inspiratory time greater than twice the patient's neural inspiratory time; Premature cycling (PC): a cycle with an inspiratory time shorter than the the neural inspiratory time; Double triggering (DT): two ventilator-delivered cycles triggered by one neural inspiration; Auto triggering (AT): a cycle delivered by the ventilator in the absence of EAdi signal.
Measured: 4 hours
Secondary outcomes (12)
Components of the Asynchrony index
Each component of the Asynchrony index will be compared between the 2 ventilatory modes.
Measured: 4 hours
Mean change in electric activity of the diaphragm (Edi)
Analyze as exploratory data of Mean delta Edi (max-min value) in NIV NAVA vs sNIPPV
Measured: 4 hours
Apnoea
Analyze as exploratory data of Frequency of apnoea
Measured: 4 hours
Desaturations
Analyze as exploratory data of Frequency of desaturations below 80%
Measured: 4 hours
Bradycardia
Analyze as exploratory data of Frequency of bradycardia < 100 bpm
Measured: 4 hours
ComfortNeo score
Analyze as exploratory data of Comfort Neo score assessed by the nurse before and after each ventilation period
Measured: 4 hours
transcutaneous PCO2
TcPCO2 modeling over time and comparison between NIV Nava and sNIPPV
Measured: 4 hours
Nava level
Description of Nava levels used during NIV Nava
Measured: 1 hour
Inspiratory pressure during sNIPPV
Description of inspiratory pressures used during sNIPPV
Measured: 1 hour
Bag-mask ventilation or re-intubation
Frequency of bag-mask ventilation or re-intubation
Measured: 4 hours
Re-intubation within 7 days
Frequency of re-intubation within 7 days of randomization
Measured: 7 days
Fi02
FiO2 changes over time during NIV NAVA and sNIPPV
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start9 Dec 2019
- Primary completion3 Mar 2021
- Study completion11 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized crossover trial in the Neonatal Intensive Care Unit
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Intercommunal Creteil
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04068558
- Sponsor's protocol ID
- EASYNNEO
- Other IDs
- 2019-A00420-57
- Acronym
- EASYNNEO
- Status last verified
- Jun 2021
- First submitted
- 22 Aug 2019
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synchronized Nasal Intermittent Positive Pressure Ventilation Versus Noninvasive Neurally Adjusted Ventilatory Assist Ventilation in Extremely Premature Infants: a Randomized Crossover Trial
- ClinicalTrials.gov ID
- NCT04068558
- Acronym / sponsor ID
- EASYNNEO / EASYNNEO
- Conditions
- Premature Birth, Ventilator Lung; Newborn
- Keywords
- neurally adjusted ventilatory assist, synchronized nasal intermittent positive pressure ventilation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Centre Hospitalier Intercommunal CreteilUniversity, hospital or other
- Study start
- 9 Dec 2019 (actual)
- Primary completion
- 3 Mar 2021 (actual)
- Study completion
- 11 Mar 2021 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to demonstrate a significant decrease in asynchrony with NIV-NAVA using the Servo n ventilator (Getinge, Sweden), as compared to abdominal triggered (Graseby capsule) synchronized nasal intermittent positive pressure ventilation (sNIPPV) using the Infant Flow CPAP device (Care Fusion, USA).
All of the data obtained can be used to develop a large-scale study aimed at reducing the rate of re-intubation in the study population (pilot study). In fact, the re-intubation criteria for extremely premature children are based on clinical criteria (desaturations, apnea, signs of respiratory control) and paraclinical criteria (FiO2, Potential hydrogen (pH), PCO2).
The results of this pilot study will help to develop an adapted methodology and to calculate a sample size to compare the 2 modes of NIV to the test on a clinical criterion: the rate of re-intubation after extubation, which is classically high in these patients.
Detailed description
The use of non-invasive ventilation has significantly reduced morbidity and mortality in premature newborns by reducing the pulmonary lesions caused by invasive ventilation. Currently, variable flow continuous positive airway pressure (CPAP) devices, such as the infant flow® driver, are considered more efficient than constant flow pressure sources. Nasal intermittent positive pressure ventilation, as compared to CPAP, might reduce the extubation failure rate, but has no impact on mortality or bronchopulmonary dysplasia. However, data is lacking on the interest of synchronization and on the effect of the different available interfaces (prongs, masks, cannulas). In addition, the ventilatory characteristics (high respiratory rate and low inspiratory effort) of the premature infant increase the risk of asynchrony between the patient and the ventilator, which is a major cause of poor tolerance for this type of ventilation.
NAVA (neurally adjusted ventilatory assist) is a recent ventilatory mode that offers proportional assistance to respiratory work based on the measured electrical activity of the diaphragm via oesophageal electrodes. It thus allows a regulation of inspiratory pressures and time by the patient him/herself. The physiological effects of NAVA have been primarily described in intubated neonates and studies have shown a significantly improved synchronization and significantly decreased inspiratory pressures in patients ventilated with NAVA compared to intermittent controlled ventilatory support. However, the currently available evidence is limited and no beneficial effect on morbidity or mortality has been identified so far .
There are few studies on noninvasive NAVA (NIV-NAVA) conducted exclusively in neonates, most of which included a limited number of patients. Only one study to date compared NIV-NAVA to another synchronized NIV mode (NIV pressure support) using the Servo-i ventilator. This prospective crossover study found a significant decrease in peak inspiratory pressure (PIP), FiO2, frequency and length of desaturations in the NIV-NAVA group.
Decreased asynchrony has been observed during NIV-NAVA as compared to pressure-support NIV In adult patients and in 6 children hospitalized in the Pediatric ICU (median age 18 months).
In premature neonates, variable flow CPAP is preferentially used. Synchronized intermittent positive pressure can be delivered using a variable flow device and a Graseby abdominal capsule. Since variable flow CPAP is considered the most efficient pressure generator, it is legitimate to compare synchronization performance of the variable flow synchronized nasal intermittent positive pressure ventilation (sNIPPV) to NIV-NAVA. This comparison has never been performed so far, to our knowledge.
We hypothesize that synchronization will be markedly improved with NIV-NAVA as compared to sNIPPV.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized crossover trial in the Neonatal Intensive Care Unit
| Arm | Type | Receives |
|---|---|---|
| VNI-NAVA/sNIPPV | Experimental | Device: VNI-NAVA/sNIPPVVentilation of the child non-invasive ventilation (VNI) NAVA then sNIPPV |
| sNIPPV/VNI-NAVA | Experimental | Device: sNIPPV/VNI-NAVAVentilation of the child sNIPPV then non-invasive ventilation (VNI) NAVA |
Who may qualify
- Ages
- 3 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Premature infants born before 28 weeks of gestation
- Corrected age below 32 weeks of gestation
- Postnatal age > or = 3 days
- Receiving NIPPV (any mode)
- Equipped with an Edi catheter
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VNI-NAVA/sNIPPVVentilation of the child in NIV-NAVA for 2 hours then ventilation of the child in sNIPPV for two hours. The ventilation periods consist of one hour of wash-out and one hour of data collection | Device | VNI-NAVA/sNIPPV |
| sNIPPV/VNI-NAVAVentilation of the child in sNIPPV for 2 hours then ventilation of the child in NIV-NAVA for two hours. The ventilation periods consist of one hour of wash-out and one hour of data collection | Device | sNIPPV/VNI-NAVA |
Primary outcome
Asynchrony index
Time frame: 4 hours
Asynchrony index as previously defined in the literature using the following parameters: Ineffective effort (IE): presence of an inspiratory electromyographic signal not followed by pressurization; Late cycling (LC): a cycle with an inspiratory time greater than twice the patient's neural inspiratory time; Premature cycling (PC): a cycle with an inspiratory time shorter than the the neural inspiratory time; Double triggering (DT): two ventilator-delivered cycles triggered by one neural inspiration; Auto triggering (AT): a cycle delivered by the ventilator in the absence of EAdi signal.
12 secondary outcomes
Components of the Asynchrony index
Time frame: 4 hours
Mean change in electric activity of the diaphragm (Edi)
Time frame: 4 hours
Apnoea
Time frame: 4 hours
Desaturations
Time frame: 4 hours
Bradycardia
Time frame: 4 hours
ComfortNeo score
Time frame: 4 hours
transcutaneous PCO2
Time frame: 4 hours
Nava level
Time frame: 1 hour
Inspiratory pressure during sNIPPV
Time frame: 1 hour
Bag-mask ventilation or re-intubation
Time frame: 4 hours
Re-intubation within 7 days
Time frame: 7 days
Fi02
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing VNI-NAVA/sNIPPV and sNIPPV/VNI-NAVA in people with Premature Birth and Ventilator Lung; Newborn, run by Centre Hospitalier Intercommunal Creteil at 1 site in France.
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 16 inclusion and 0 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 8 Jun 2021. 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 France. 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?
Asynchrony index (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Jun 2021.