NCT03181958

Brief Summary

Respiratory distress syndrome (RDS) is the main cause of respiratory failure in preterm neonates, its incidence varying from 80% to 25% depending on gestational age.When optimal prenatal care is provided, the best approach to treat RDS, according to several recent trials,consists in providing continuous positive airway pressure (CPAP) from the first minutes of life using short binasal prongs or masks, followed by early selective surfactant administration for babies with worsening oxygenation and/or increasing work of breathing. Any effort should be done to minimize the time under invasive mechanical ventilation (IMV).Nonetheless, clinical trials have shown that a relevant proportion of preterm neonates fails this approach and eventually need IMV.The duration of IMV is a well known risk factor for the development of broncho-pulmonary dysplasia (BPD) - a condition associated with significant morbidity and mortality. To minimize the duration of IMV, various non invasive respiratory support modalities are available in neonatal intensive care units (NICU). CPAP is presently the most common technique used in this regard. However, a systematic review has shown that non-invasive positive pressure ventilation (NIPPV) reduces the need for IMV (within one week from extubation) more effectively than NCPAP, although it is not clear if NIPPV may reduce need for intubation longterm and it seems to have no effect on BPD and mortality. NIPPV main drawback is the lack of synchronization, which is difficult to be accurately achieved and is usually unavailable. A more recent alternative technique is non-invasive high frequency oscillatory ventilation (NHFOV) which consists on the application of a bias flow generating a continuous distending positive pressure with oscillations superimposed on spontaneous tidal breathing with no need for synchronization. The physiological, biological and clinical details about NHFOV have been described elsewhere. To date, there is only one small observational uncontrolled study about the use of NHFOV after extubation in preterm infants. Other relatively small case series or retrospective cohort studies suggested safety, feasibility and possible usefulness of NHFOV and have been reviewed elsewhere.The only randomized trial published so far compared NHFOV to biphasic CPAP,in babies failing CPAP and it has been criticized for methodological flaws and for not taking into account respiratory physiology.An European survey showed that, despite the absence of large randomized clinical trials, NHFOV is quite widely used, at least in some Countries and no major side effects are reported, although large data about NHFOV safety are lacking. This may be due to the relative NHFOV easiness of use but evidence-based and physiology-driven data are warranted about this technique.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,493

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Dec 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 28, 2017

Completed
12 days until next milestone

First Posted

Study publicly available on registry

June 9, 2017

Completed
6 months until next milestone

Study Start

First participant enrolled

December 1, 2017

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2021

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2021

Completed
3 months until next milestone

Results Posted

Study results publicly available

September 30, 2021

Completed
Last Updated

September 30, 2021

Status Verified

September 1, 2021

Enrollment Period

3.5 years

First QC Date

May 28, 2017

Results QC Date

July 28, 2021

Last Update Submit

September 2, 2021

Conditions

Intubated Infants Were Intend to Extubation Using Noninvasive Ventilation Strategies

Keywords

nasal high frequency oscillation ventilation(NHFOV)nasal continuous positive airway pressure(NCPAP)nasal intermittent positive pressure ventilation（NIPPV）neonatal respiratory distress syndrome(NRDS)preterm infants

Outcome Measures

Primary Outcomes (3)

  • Duration of Invasive Mechanical Ventilation

    the total days of the baby supported with the ventilator

    up to 8 weeks

  • Ventilator-free Days

    non-invasive ventilation was need after extubation

    up to 8 weeks

  • Number of Babies With Reintubation

    the total numbers of the baby supported with ventilator

    up to 8 weeks

Secondary Outcomes (10)

  • Number of Participants With Airleaks

    up to 8 weeks

  • Number of Participants With Bronchopulmonary Dysplasia(BPD)

    at gestational age of 36 weeks or at discharge

  • Number of Participants With Retinopathy of Prematurity> 2nd Stage

    up to 8 weeks

  • Number of Participants With Neonatal Necrotizing Enterocolitis≥ 2nd Stage

    up to 8 weeks

  • Number of Participants With Intraventricular Hemorrhage>2nd Grade

    up to 8 weeks

  • +5 more secondary outcomes

Study Arms (3)

NHFOV

EXPERIMENTAL

neonates assigned to NHFOV will be started with the following boundaries: a) Paw of 10 cmH2O (can be changed in steps of 1 cmH2O within the range range 5- 16cmH2O); Paw will be titrated (within the range) according to open lung strategy, performing alveolar recruitment, similar to what is done in endotracheal high frequency oscillatory ventilation targeting a FiO2≤25-30%. Maximal allowed FiO2 will be 0.40 and SpO2 targets will be 90%-95%. b) frequency of 10Hz(can be changed in steps of 1Hz within the range 8-12Hz). c)Inspiratory time 50% (1:1).d)amplitude 25 cmH2O(can be changed in steps of 5 cmH2O within the range 25-50 cmH2o; amplitude will be titrated according to PaCO2.

Device: NHFOV

NCPAP

ACTIVE COMPARATOR

Neonates assigned to the CPAP group were initiated on a pressure of 5 cmH2O. CPAP can be raised in steps of 1 cmH2O up to 8 cmH2O. If this is not enough to maintain SpO2 between 90% and 95%, FiO2 will be added up to 0.40.

Device: NCPAP

NIPPV

EXPERIMENTAL

neonates assigned to the NIPPV group will be started with the following parameters: a) positive end-expiratory pressure (PEEP) of 4 cmH2O (can be raised in steps of 1 cmH2O to max 8 cmH2O, according to the oxygenation).b)Peak Inspiratory Pressure (PIP) of 15 cmH2O (can be raised in steps of 1 cmH2O to max 25 cmH2O, according to oxygenation,PaCO2 levels and the chest expansion); maximal allowed FiO2 will be 0.40 and SpO2 targets will be 90-95%. c) inspiratory time (IT) will be 0.45 - 0.5 sec(according to clinicians' evaluation of leaks and the appearance of the pressure curve: a small pressure plateau is required and flow may be set accordingly) and rate will be started at 30 bpm (can be raised in steps of 5 bpm to max 50 bpm, according to PaCO2 levels).

Device: NIPPV

Interventions

NHFOVDEVICE

Nasal high frequency oscillation ventilation (NHFOV) is used as the noninvasive supporting mode after extubation.

NHFOV
NCPAPDEVICE

Nasal continuous positive airway pressure(NCPAP) is used as the noninvasive supporting mode after extubation.

NCPAP
NIPPVDEVICE

Nasal intermittent positive pressure ventilation(NIPPV) is used as the noninvasive supporting mode after extubation.

NIPPV

Eligibility Criteria

Age30 Minutes - 1 Month
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • gestational age between 25+0 and 32+6 weeks;
  • birth weight more than 600 g;
  • supported with any type of endotracheal ventilation;
  • Has not had first attempt at extubation(extubation readiness requires fulfilling of all the following criteria: a. Having received at least one loading dose of 20 mg/kg and 5 mg/kg daily maintenance dose of caffeine citrate; b. pH\>7.20 PaCO2\<=60 mmHg (these may be evaluated by arterialized capillary blood gas analysis or appropriately calibrated transcutaneous monitors. Venous blood gas values cannot be used); c. Paw \<=7-8 cmH2O; d. FiO2\<=0.30; e. sufficient spontaneous breathing effort, as per clinical evaluation).;
  • Obtained parental consent. Informed consent will be obtained antenatally or upon neonatal intensive care unit admission.;

You may not qualify if:

  • major congenital anomalies or chromosomal abnormalities;
  • Presence of neuromuscular disease;
  • Upper respiratory tract abnormalities; ;
  • need for surgery known before the first extubation;
  • Grade IV-intraventricular haemorrhage (IVH) occurring before the first extubation
  • congenital lung diseases or malformations or pulmonary hypoplasia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Chongqing, Chongqing Municipality, 400042, China

Location

Related Publications (3)

  • Zhu X, Li F, Shi Y, Feng Z, De Luca D; Nasal Oscillation Post-Extubation (NASONE) Study Group. Effectiveness of Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation vs Noninvasive High-Frequency Oscillatory Ventilation as Support After Extubation of Neonates Born Extremely Preterm or With More Severe Respiratory Failure: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2321644. doi: 10.1001/jamanetworkopen.2023.21644.

    PMID: 37399009DERIVED

  • Zhu X, Qi H, Feng Z, Shi Y, De Luca D; Nasal Oscillation Post-Extubation (NASONE) Study Group. Noninvasive High-Frequency Oscillatory Ventilation vs Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation as Postextubation Support for Preterm Neonates in China: A Randomized Clinical Trial. JAMA Pediatr. 2022 Jun 1;176(6):551-559. doi: 10.1001/jamapediatrics.2022.0710.

    PMID: 35467744DERIVED

  • Shi Y, De Luca D; NASal OscillatioN post-Extubation (NASONE) study group. Continuous positive airway pressure (CPAP) vs noninvasive positive pressure ventilation (NIPPV) vs noninvasive high frequency oscillation ventilation (NHFOV) as post-extubation support in preterm neonates: protocol for an assessor-blinded, multicenter, randomized controlled trial. BMC Pediatr. 2019 Jul 26;19(1):256. doi: 10.1186/s12887-019-1625-1.

    PMID: 31349833DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn

Condition Hierarchy (Ancestors)

Respiratory Distress SyndromeLung DiseasesRespiratory Tract DiseasesRespiration DisordersInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

Title
Dr.Yuan Shi
Organization
Children's Hospital of Chongqing Medical University
shiyuan@hospital.cqmu.edu.cn
+86 23 68757731

Study Officials

  • Shi Yuan, PhD,MD

    Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Blinding towards the caregivers is impossible and blinding towards the patients makes no sense. However, outcomes' assessors will be blinded, as endpoints will be recorded by investigators not involved in patients' care. An assessor per each participating NICU will be nominated. Moreover, investigators performing the final statistical analyses will be blinded to the treatment allocation, as data collected by assessors will be inserted in the dedicated website and the arms' allocation will be re-coded.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: When the neonate had fulfilled the extubation criteria, extubation will took place with a gentle intratracheal suction. Upper airways will then be suctioned and intervention will be started immediately as follows: Ventilators * CPAP: CPAP will be provided by either variable flow or continuous flow devices, as there is no evidence that one type of CPAP generator would be better than any other. * NIPPV: NIPPV will be provided by any type of neonatal ventilator. Synchronization will not be applied, as many currently marketed neonatal ventilators usually do not provide it for NIPPV. * NHFOV: NHFOV will only be provided with piston/membrane oscillators able to provide a real oscillatory pressure with active expiratory phase (that is, Acutronic FABIAN-III, SLE 5000, Loweinstein Med LEONI+, Sensormedics 3100A). Other machines providing high frequency ventilations will not be used. Importantly, the randomization should be done within one hour from the extubation to avoid bias.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
director

Study Record Dates

First Submitted

May 28, 2017

First Posted

June 9, 2017

Study Start

December 1, 2017

Primary Completion

May 31, 2021

Study Completion

June 30, 2021

Last Updated

September 30, 2021

Results First Posted

September 30, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will share

Every researchers can obtain the IPD after the study completely.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
At Oct-22,2017,Suzhou,PR.China.

Locations

CN(1)