Nasal HFOV Versus Nasal CPAP to Reduce Post-extubation pCO2

Not Applicable

Terminated

Conditions: Respiratory Distress Syndrome, Newborn
Respiratory Tract Diseases

Interventions: Device: nHFOV
Device: nCPAP

Registration Number: NCT02340299

Lead Sponsor: Charite University, Berlin, Germany

Brief Summary: To investigate whether nasal high frequency oscillation ventilation (nHFOV) immediately after extubation reduces the arterial partial pressure of carbon dioxide (paCO2) at 72 hours after extubation in comparison with nasal continuous positive airway pressure (nCPAP) in very low birth weight infants (VLBWs).

Detailed Description: Randomized controlled clinical trial comparing nHFOV vs nCPAP immediately after extubation of VLBW infants.

Intervention and treatment protocol as described for the two study arms.

Definition of treatment failure (infant meets at least one criterion):

* Sustained pCO2 \>80 mmHg and pH \<7.20 confirmed by arterial or capillary blood gas analysis in spite of optimized non-invasive respiratory support with maximum settings as defined above.

* Fraction of inspired oxygen (FiO2) \>0.6 to maintain peripheral oxygen saturation as measured by pulse oximetry (SpO2) at 90-94% in spite of optimized non-invasive respiratory support with maximum settings as defined above.

* Reintubation (study patients may be intubated at any time, due to clinical considerations, with or without reaching another criterion of "treatment failure").

Sample size:

Assuming a variability of the paCO2 as previously reported for difficult-to-wean preterm infants in our unit (Czernik C, J Matern Fetal Neonatal Med 2012) and a treatment failure rate of 22% within 72 hours after extubation, we calculated a sample size of 34 patients in each study arm to detect a difference in the paCO2 of 7 mmHg, using a two-sided significance of 0.05 and a power of 0.8.

Randomization:

Sequence generation by an independent statistician and a study nurse. Block randomization using at least two different block sizes. Allocation concealment using sequentially numbered opaque sealed envelopes.

Data monitoring:

By an independent statistician.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Gestational age <32+0 weeks
Birth weight <1500 g
Received mechanical ventilation via an endotracheal tube for ≥120 h
Caffeine treatment according to unit guidelines
paCO2 <65 mmHg with pH >7.2
FiO2 25-40% to maintain SpO2 at 90-94%.
Time-cycled, pressure-controlled ventilation: PIP ≤22 cm H2O, PEEP ≤6 cm H2O; Volume guarantee ventilation: Working Ppeak ≤22 cm H2O, PEEP ≤6 cm H2O; High frequency oscillation ventilation: Pmean ≤12 cm H2O, Amplitude ≤30 cm H2O
Decision of the attending clinician to extubate

Exclusion Criteria

Major congenital malformation requiring surgery
Duct-dependent congenital heart disease
Neuromuscular disease
Participation in another randomized controlled trial
Death before reaching the eligibility criteria
Hydrocortisone treatment at the time of enrolment
Chronological age >28 days

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
nHFOV	nHFOV	Immediately after extubation, nHFOV is provided via binasal prongs. Ventilator settings: Frequency set at 10 Hz, I:E ratio 33:66, amplitude 20 cm H2O, Pmean 8 cm H2O, flow 7 l/min. Set FiO2 to maintain SpO2 at 90-94%. The weaning process is left to the discretion of the attending physician. Maximum amplitude 30 cm H2O, minimum frequency 9 Hz, maximum Pmean 8 cm H2O. For infants in the nHFOV-group who "fail" nHFOV (see definition below), but do not need immediate reintubation, a non-invasive "Rescue-Treatment" may be provided. The decision to attempt "Rescue-Treatment", the mode of respiratory support and the ventilator settings used are at the discretion of the attending clinician.
nCPAP	nCPAP	Immediately after extubation, nCPAP is provided via binasal prongs. Ventilator settings: CPAP level set at 8 cm H2O, flow 7 l/min. Set FiO2 to maintain SpO2 at 90-94%. The weaning process is left to the discretion of the attending physician. Maximum CPAP level 8 cm H2O, maximum flow 8 l/min. For infants in the nCPAP-group who "fail" nCPAP (see definition below), but do not need immediate reintubation, "Rescue-nHFOV" via binasal prongs may be provided. The decision to attempt "Rescue-nHFOV" and the ventilator settings used are at the discretion of the attending clinician.

Primary Outcome Measures

Name	Time	Method
paCO2 at 72 h After Extubation	64 h to 80 h	Partial pressure of arterial carbon dioxide assessed between 64 and 80 hours, and on average 72 hours.

Secondary Outcome Measures

Name	Time	Method
paCO2 at 2 h After Extubation	within the first 6 h after extubation
Base Excess at 2 h After Extubation	within the first 6 h after extubation
Other Adverse Effects	until discharge	Incidences of the following adverse effects: Intraventricular hemorrhage III°-IV° (Papile), surgical necrotizing enterocolitis, pneumothorax, pulmonary interstitial emphysema, persistent ductus arteriosus requiring surgical closure, retinopathy of prematurity requiring laser treatment and/or injection of bevacizumab, death or moderate to severe bronchopulmonary dysplasia (Jobe) at 36 weeks' gestational age, periventricular leukomalacia
Duration of Respiratory Support	until discharge	Total duration of mechanical ventilation, total duration of supplemental oxygen, number of infants discharged with home oxygen
pH at 2 h After Extubation	within the first 6 h after extubation
pH at 72 h After Extubation	64-80 h after extubation
Treatment Failure	within 7 days after extubation	Defined as the number of patients reaching the criterion of "treatment failure"
Base Excess at 72 h After Extubation	64-80 h after extubation
Highly Viscous Secretions	within 72 hours after extubation	Defined as the documented number of episodes of airway obstruction due to highly viscous secretions per patient
paO2 at 2 h After Extubation	within the first 6 h after extubation
paO2 at 72 h After Extubation	64-80 h after extubation
Successful Extubation	72 h after extubation	Defined as the number of patients breathing spontaneously in their assigned treatment group for ≥72h without reaching the criterion of "treatment failure"
Reintubation	within 7 days after extubation	Defined as the number of patients being reintubated