NCT03181958

A Trial Comparing Noninvasive Ventilation Strategies in Preterm Infants Following Extubation

Completed NA Results posted Last updated 30 September 2021

What this trial tests

NA trial testing NHFOV in Intubated Infants Were Intend to Extubation Using Noninvasive Ventilation Strategies in 1,493 participants. Completed in 30 June 2021.

Timeline

1 December 2017

Primary endpoint
31 May 2021

30 June 2021

Quick facts

Lead sponsor	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	1,493
Start date	1 December 2017
Primary completion	31 May 2021
Estimated completion	30 June 2021
Sites	1 location across China

Drugs / interventions tested

• NHFOV
• NCPAP — full drug profile →
• NIPPV

Conditions studied

• Intubated Infants Were Intend to Extubation Using Noninvasive Ventilation Strategies — all drugs for Intubated Infants Were Intend to Extubation Using Noninvasive Ventilation Strategies →

Sponsor

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

Who can join

Adults 30 Minutes to 1 Month, any sex, with Intubated Infants Were Intend to Extubation Using Noninvasive Ventilation Strategies. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Duration of Invasive Mechanical Ventilation Primary · up to 8 weeks

the total days of the baby supported with the ventilator

Group	Value	95% CI
NHFOV	6.3	± 6.0
NCPAP	7.8	± 7.2
NIPPV	7.3	± 9.2

Ventilator-free Days Primary · up to 8 weeks

non-invasive ventilation was need after extubation

Group	Value	95% CI
NHFOV	34	17 – 52
NCPAP	32	20 – 45
NIPPV	35	21 – 52

Number of Babies With Reintubation Primary · up to 8 weeks

the total numbers of the baby supported with ventilator

Group	Value	95% CI
NHFOV	63
NCPAP	123
NIPPV	84

Number of Participants With Airleaks Secondary · up to 8 weeks

airleaks was diagnosed after extubation

Group	Value	95% CI
NHFOV	4
NCPAP	3
NIPPV	9

Number of Participants With Bronchopulmonary Dysplasia(BPD) Secondary · at gestational age of 36 weeks or at discharge

Bronchopulmonary dysplasia was defined, according to National Institutes of Health (NIH) criteria, by the receipt of any form of positive-airway-pressure support or a requirement for supplemental oxygen at 36 weeks. A requirement for supplemental oxygen at 36 weeks was defined as an FiO2 of 0.30 or more or

Group	Value	95% CI
NHFOV	163
NCPAP	184
NIPPV	182

Number of Participants With Retinopathy of Prematurity> 2nd Stage Secondary · up to 8 weeks

Retinopathy of prematurity\> 2nd stage was diagnosed after extubation

Group	Value	95% CI
NHFOV	63
NCPAP	74
NIPPV	72

Number of Participants With Neonatal Necrotizing Enterocolitis≥ 2nd Stage Secondary · up to 8 weeks

Neonatal necrotizing enterocolitis≥ 2nd stage was diagnosed after extubation

Group	Value	95% CI
NHFOV	33
NCPAP	24
NIPPV	36

Number of Participants With Intraventricular Hemorrhage>2nd Grade Secondary · up to 8 weeks

Intraventricular hemorrhage\>2nd grade was diagnosed after extubation

Group	Value	95% CI
NHFOV	48
NCPAP	63
NIPPV	59

Number of Participants With Need for Postnatal Steroids Secondary · up to 8 weeks

steroids was used for chronic lung disease

Group	Value	95% CI
NHFOV	63
NCPAP	77
NIPPV	98

In-hospital Mortality Secondary · up to 8 weeks

the baby died in hospital

Group	Value	95% CI
NHFOV	8
NCPAP	5
NIPPV	4

Composite Mortality/BPD Secondary · up to 8 weeks

the baby was dead or diagnosed with BPD.

Group	Value	95% CI
NHFOV	171
NCPAP	189
NIPPV	186

Weekly Weight Gain Secondary · during hospitalization for the first 4 weeks of life or until NICU discharge whichever came first, an average of 1 month

Weekly weight gain (in grams/day) for the first 4 weeks of life or until NICU discharge, whichever comes first

Group	Value	95% CI
NHFOV	13.0	± 5.3
NCPAP	12.1	± 4.9
NIPPV	12.4	± 6.4

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 8 weeks. Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NHFOV

Serious: 0/480 (0%)

Deaths: 8/480

NCPAP

Serious: 0/480 (0%)

Deaths: 5/480

NIPPV

Serious: 0/480 (0%)

Deaths: 4/480

Other adverse events (1 terms — click to expand)

Reaction	System	NHFOV	NCPAP	NIPPV
Nasal skin injury	Injury, poisoning and procedural complications	—	—	—

Data from ClinicalTrials.gov NCT03181958 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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.
   Zhu X, Qi H, Feng Z, Shi Y, et al · · 2022 · cited 47× · PMID 35467744 · DOI 10.1001/jamapediatrics.2022.0710
2. Noninvasive high-frequency oscillatory ventilation as respiratory support in preterm infants: a meta-analysis of randomized controlled trials.
   Li J, Li X, Huang X, Zhang Z. · · 2019 · cited 38× · PMID 30876411 · DOI 10.1186/s12931-019-1023-0
3. 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
   Shi Y, De Luca D, NASal OscillatioN post-Extubation (NASONE) study group. · · 2019 · cited 22× · PMID 31349833 · DOI 10.1186/s12887-019-1625-1
4. 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
   Zhu X, Li F, Shi Y, Feng Z, et al · · 2023 · cited 14× · PMID 37399009 · DOI 10.1001/jamanetworkopen.2023.21644
5. Non-invasive high-frequency ventilation in newborn infants with respiratory distress.
   Abdel-Latif ME, Tan O, Fiander M, Osborn DA. · · 2024 · cited 11× · PMID 38695628 · DOI 10.1002/14651858.cd012712.pub2
6. Noninvasive high-frequency oscillation ventilation as post- extubation respiratory support in neonates: Systematic review and meta-analysis.
   Prasad R, Saha B, Sk MH, Sahoo JP, et al · · 2024 · cited 3× · PMID 39078848 · DOI 10.1371/journal.pone.0307903