Respiratory Distress Syndrome, Newborn, Respiratory Tract Diseases
Conditions
Keywords
High Frequency Oscillation Ventilation, Nasal Continuous Positive Airway Pressure, Airway Extubation, Prematurity
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.
Interventions
DEVICEnHFOV
Extubation to ventilator-derived nHFOV using binasal prongs
DEVICEnCPAP
Extubation to ventilator-derived nCPAP using binasal prongs
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Days to 28 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Reintubation | within 7 days after extubation | Defined as the number of patients being reintubated |
| 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 |
| 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 | — |
| 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 | — |
| 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 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | 72 h after switch to rescue treatment | Defined as spontaneous breathing for ≥72h after starting rescue therapy, without reaching the criterion of treatment failure |
| 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 | — |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
nHFOV: Extubation to ventilator-derived nHFOV using binasal prongs | 4 |
| 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.
nCPAP: Extubation to ventilator-derived nCPAP using binasal prongs | 2 |
| Total | 6 |
Baseline characteristics
| Characteristic | nCPAP | Total | nHFOV |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 6 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 16 days | 17.5 days | 19 days |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Germany | 2 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 2 / 4 | 0 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 |
Outcome results
Primary
paCO2 at 72 h After Extubation
Partial pressure of arterial carbon dioxide assessed between 64 and 80 hours, and on average 72 hours.
Time frame: 64 h to 80 h
Population: In patients that were reintubated within 72 h, the primary outcome, paCO2 72 h after extubation, could not be assessed. In the nCPAP group, all patients had to be reintubated within 72 h. The primary outcome, paCO2 72 h after extubation, could therefore only be assessed in the nHFOV group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| nHFOV | paCO2 at 72 h After Extubation | 65.5 mmHg |
Secondary
Base Excess at 2 h After Extubation
Time frame: within the first 6 h after extubation
Secondary
Base Excess at 72 h After Extubation
Time frame: 64-80 h after extubation
Secondary
Duration of Respiratory Support
Total duration of mechanical ventilation, total duration of supplemental oxygen, number of infants discharged with home oxygen
Time frame: until discharge
Secondary
Highly Viscous Secretions
Defined as the documented number of episodes of airway obstruction due to highly viscous secretions per patient
Time frame: within 72 hours after extubation
Secondary
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
Time frame: until discharge
Secondary
paCO2 at 2 h After Extubation
Time frame: within the first 6 h after extubation
Secondary
paO2 at 2 h After Extubation
Time frame: within the first 6 h after extubation
Secondary
paO2 at 72 h After Extubation
Time frame: 64-80 h after extubation
Secondary
pH at 2 h After Extubation
Time frame: within the first 6 h after extubation
Secondary
pH at 72 h After Extubation
Time frame: 64-80 h after extubation
Secondary
Reintubation
Defined as the number of patients being reintubated
Time frame: within 7 days after extubation
Secondary
Successful Extubation
Defined as the number of patients breathing spontaneously in their assigned treatment group for ≥72h without reaching the criterion of treatment failure
Time frame: 72 h after extubation
Secondary
Treatment Failure
Defined as the number of patients reaching the criterion of treatment failure
Time frame: within 7 days after extubation
Other Pre-specified
Base Excess at 2 h After Switch to Rescue Treatment
Time frame: within the first 6 h after switch to rescue treatment
Other Pre-specified
paCO2 at 2 h After Switch to Rescue Treatment
Time frame: within the first 6 h after switch to rescue treatment
Other Pre-specified
paO2 at 2 h After Switch to Rescue Treatment
Time frame: within the first 6 h after switch to rescue treatment
Other Pre-specified
pH at 2 h After Switch to Rescue Treatment
Time frame: within the first 6 h after switch to rescue treatment
Other Pre-specified
Successful Rescue
Defined as spontaneous breathing for ≥72h after starting rescue therapy, without reaching the criterion of treatment failure
Time frame: 72 h after switch to rescue treatment