Nasal HFOV Versus Nasal CPAP to Reduce Post-extubation pCO2

Nasal High Frequency Oscillation Ventilation Versus Nasal Continuous Positive Airway Pressure to Reduce Post-extubation pCO2 in Very Low Birth Weight Infants: a Randomized Controlled Trial

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).

Study Overview

• Status: Terminated
• Conditions: Respiratory Tract Diseases; Respiratory Distress Syndrome, Newborn
• Intervention / Treatment: Device: nHFOV; Device: nCPAP

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Dpt. of Neonatology, Charité - Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 days to 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: nHFOV; Extubation to ventilator-derived nHFOV using binasal prongs
Active Comparator: 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.	Device: nCPAP; Extubation to ventilator-derived nCPAP using binasal prongs

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pH at 2 h After Extubation		within the first 6 h after extubation
paO2 at 2 h After Extubation		within the first 6 h after extubation
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
pH at 72 h After Extubation		64-80 h after extubation
paO2 at 72 h After Extubation		64-80 h after extubation
Base Excess at 72 h After Extubation		64-80 h after extubation
Successful Extubation	Defined as the number of patients breathing spontaneously in their assigned treatment group for ≥72h without reaching the criterion of "treatment failure"	72 h after extubation
Treatment Failure	Defined as the number of patients reaching the criterion of "treatment failure"	within 7 days after extubation
Reintubation	Defined as the number of patients being reintubated	within 7 days after extubation
Highly Viscous Secretions	Defined as the documented number of episodes of airway obstruction due to highly viscous secretions per patient	within 72 hours after extubation
Other Adverse Effects	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	until discharge
Duration of Respiratory Support	Total duration of mechanical ventilation, total duration of supplemental oxygen, number of infants discharged with home oxygen	until discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pH at 2 h After Switch to "Rescue Treatment"		within the first 6 h after switch to "rescue treatment"
paO2 at 2 h After Switch to "Rescue Treatment"		within the first 6 h after switch to "rescue treatment"
paCO2 at 2 h After Switch to "Rescue Treatment"		within the first 6 h after switch to "rescue treatment"
Base Excess at 2 h After Switch to "Rescue Treatment"		within the first 6 h after switch to "rescue treatment"
Successful Rescue	Defined as spontaneous breathing for ≥72h after starting "rescue" therapy, without reaching the criterion of "treatment failure"	72 h after switch to "rescue" treatment

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Christoph Czernik, MD PhD, Charite University, Berlin, Germany

Publications and helpful links

General Publications

• Fischer HS, Buhrer C, Czernik C. Hazards to avoid in future neonatal studies of nasal high-frequency oscillatory ventilation: lessons from an early terminated trial. BMC Res Notes. 2019 Apr 25;12(1):237. doi: 10.1186/s13104-019-4268-2.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: January 10, 2015
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (Estimate): January 16, 2015

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Prematurity; Nasal Continuous Positive Airway Pressure; Airway Extubation; High Frequency Oscillation Ventilation
• Additional Relevant MeSH Terms: Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Tract Diseases
• Other Study ID Numbers: EA2/011/12