Respiratory Distress Syndrome, NewbornNCT02340299
Nasal HFOV Versus Nasal CPAP to Reduce Post-extubation pCO2
A study testing nHFOV and nCPAP in people with Respiratory Distress Syndrome, Newborn and Respiratory Tract Diseases, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 5 to 28 days
- Conditions the study is for
- Respiratory Distress Syndrome, Newborn, Respiratory Tract Diseases
- What is being tested?
- nHFOV and nCPAP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jan 2015to 31 Dec 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Dpt. of Neonatology, Charité - Universitätsmedizin Berlin
Berlin
About this study
Official title: 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).
Read the 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.
- Being tested
- nHFOV, nCPAP
- Keywords
- High Frequency Oscillation Ventilation, Nasal Continuous Positive Airway Pressure, Airway Extubation, Prematurity
- Medical subject headings
- Respiratory Distress Syndrome, Newborn, Respiratory Tract Diseases, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nHFOVDevice
Extubation to ventilator-derived nHFOV using binasal prongs
nCPAPDevice
Extubation to ventilator-derived nCPAP using binasal prongs
| Study group | Role | What they receive |
|---|---|---|
| nHFOV | Experimental | 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. Receives: Device: nHFOV |
| nCPAP | Active comparator | 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. Receives: Device: nCPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
paCO2 at 72 h After Extubation
Partial pressure of arterial carbon dioxide assessed between 64 and 80 hours, and on average 72 hours.
Measured: 64 h to 80 h
Secondary outcomes (13)
pH at 2 h After Extubation
Measured: within the first 6 h after extubation
paO2 at 2 h After Extubation
Measured: within the first 6 h after extubation
paCO2 at 2 h After Extubation
Measured: within the first 6 h after extubation
Base Excess at 2 h After Extubation
Measured: within the first 6 h after extubation
pH at 72 h After Extubation
Measured: 64-80 h after extubation
paO2 at 72 h After Extubation
Measured: 64-80 h after extubation
Base Excess at 72 h After Extubation
Measured: 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"
Measured: 72 h after extubation
Treatment Failure
Defined as the number of patients reaching the criterion of "treatment failure"
Measured: within 7 days after extubation
Reintubation
Defined as the number of patients being reintubated
Measured: 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
Measured: 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
Measured: until discharge
Duration of Respiratory Support
Total duration of mechanical ventilation, total duration of supplemental oxygen, number of infants discharged with home oxygen
Measured: until discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2015 (estimated)
- Study start1 Jan 2015
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome, NewbornStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christoph Czernik, Charite University, Berlin, Germany
- Investigators
- Christoph Czernik, MD PhD, Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02340299
- Sponsor's protocol ID
- EA2/011/12
- Status last verified
- Jul 2020
- First submitted
- 10 Jan 2015
- Last updated
- 5 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 31023363
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02340299
- Acronym / sponsor ID
- EA2/011/12
- Keywords
- High Frequency Oscillation Ventilation, Nasal Continuous Positive Airway Pressure, Airway Extubation, Prematurity
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- 1 Jan 2015 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 16 Jan 2015 (estimated)
- Results
- Posted 5 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nHFOV | Experimental | Device: nHFOVImmediately 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 | Active comparator | Device: nCPAPImmediately 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. |
Who may qualify
- Ages
- 5 to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (7 listed)
- Major congenital malformation requiring surgery
- Duct-dependent congenital heart disease
- Neuromuscular disease
- Participation in another randomized controlled trial
- Death before reaching the eligibility criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nHFOVExtubation to ventilator-derived nHFOV using binasal prongs | Device | nHFOV |
| nCPAPExtubation to ventilator-derived nCPAP using binasal prongs | Device | nCPAP |
Primary outcome
paCO2 at 72 h After Extubation
Time frame: 64 h to 80 h
Partial pressure of arterial carbon dioxide assessed between 64 and 80 hours, and on average 72 hours.
13 secondary outcomes
pH at 2 h After Extubation
Time frame: within the first 6 h after extubation
paO2 at 2 h After Extubation
Time frame: within the first 6 h after extubation
paCO2 at 2 h After Extubation
Time frame: within the first 6 h after extubation
Base Excess at 2 h After Extubation
Time frame: within the first 6 h after extubation
pH at 72 h After Extubation
Time frame: 64-80 h after extubation
paO2 at 72 h After Extubation
Time frame: 64-80 h after extubation
Base Excess at 72 h After Extubation
Time frame: 64-80 h after extubation
Successful Extubation
Time frame: 72 h after extubation
Treatment Failure
Time frame: within 7 days after extubation
Reintubation
Time frame: within 7 days after extubation
Highly Viscous Secretions
Time frame: within 72 hours after extubation
Other Adverse Effects
Time frame: until discharge
Duration of Respiratory Support
Time frame: until discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31023363Fischer 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.
Related trials for Respiratory Distress Syndrome, Newborn
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Recruiting
REspiratory MEchanics for Delivering Individualised Exogenous Surfactant
Respiratory Distress Syndrome in Premature Infant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christoph Czernik, MD PhD principal investigator
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing nHFOV and nCPAP in people with Respiratory Distress Syndrome, Newborn and Respiratory Tract Diseases, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
paCO2 at 72 h After Extubation (time frame: 64 h to 80 h). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02340299, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2020.