Respiratory Distress Syndrome
Conditions
Keywords
Nasal high flow therapy, Continuous positive airway pressure
Brief summary
Premature babies often need help breathing for a longer period of time. Traditionally, this is done with a breathing aid called NCPAP (nasal continuous positive airway pressure). This treatment is safe and effective, but it is very time-consuming and can sometimes have side effects. In the present research project, the investigators want to find out whether another type of breathing aid called NHF (nasal high flow therapy) is just as effective for stable premature babies. The investigators suspect that NHF is just as effective, but easier to use and more comfortable.
Detailed description
This is a multi center parallel group three arm randomized controlled clinical trial investigating cardiorespiratory stability in stable preterm infants receiving NHF. Currently, NCPAP remains the gold standard for administration of prolonged non-invasive ventilatory support in very preterm infants. NHF is a promising method for tailored, less invasive long-term ventilatory support for preterm infants. If ventilatory support with NHF is similarly effective to conventional NCPAP in stable preterm infants, clinicians are likely to adopt this method for widespread clinical use because of its improved comfort and potential other benefits. Primary aim of this trial is to examine cardiorespiratory stability in preterm infants treated with two commonly used NHF flowrates (Interventional group 1 and 2) in comparison to NCPAP (Comparator). Secondary aim is to examine potential comfort-related beneficial effects of NHF.
Interventions
OTHERNHF high
Nasal high flow therapy 8L/min.
OTHERNHF low
Nasal high flow therapy 6L/min.
OTHERNCPAP
Nasal continuous positive airway pressure 6 cm H20
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Masking description
Due to the nature of the study design masking is not possible.
Eligibility
Sex/Gender
ALL
Age
23 Weeks to 31 Weeks
Healthy volunteers
No
Inclusion criteria
Inclusion if all apply. * Preterm infants up to 31+6 weeks GA admitted to the Division of Neonatology at Inselspital Bern, Switzerland or Division of Neonatology at the University Medical Center of the Johannes Gutenberg-University Mainz, Germany (inborn or outborn) * \>2nd day of life (defined as date day) * Stable on NCPAP 6 cm H2O for ≥ 24 hours, defined as: * ≤ 2 apneas with concomitant bradycardias (\<100/min) per hour for the previous 6 hours * FiO2 ≤ 0.3 and not increasing * No significant chest recessions (Silverman Score \< 5) * Respiratory rate ≤ 60/min * No need for intermittent positive pressure ventilation * Parents with an age 18+ years * Written parental informed consent (or other legal representative)
Exclusion criteria
Exclusion if any applies. * Significant fetal anomalies * Primary palliative care * Stable on NCPAP 6 cm H2O according to stability criteria for more than 120 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment failure | 24 hours | Treatment failure is a composite outcome defined as meeting one of the following treatment failure criteria within 24 hours of starting of intervention: 1. \>2 apneas with concomitant bradycardias (\<100/min) per hour for \> 1 hour or 2. FiO2 \> 0.3 consistently for \> 1 hour or 3. Significant chest recessions (Silverman Score ≥ 5) for \> 1 hour or 4. Respiratory rate \> 60/min consistently for \> 1 hour or 5. Any need for intermittent positive pressure ventilation The presence of Treatment failure within 24 hours of starting of intervention will be documented (dichotomous outcome; yes/no). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apneas and bradycardias | 24 hours | The total frequency of apneas and bradycardias (\<100/min) within 24 hours of starting of intervention will be documented. |
| Heart rate (HR) | 24 hours | The mean HR within 24 hours of starting of intervention will be documented. |
| Incidence of Bronchopulmonary dysplasia (BPD) | At 36 weeks PMA | The incidence with specification of severity of BPD at 36 weeks PMA will be documented. BPD is a form of chronic lung disease (CLD). BPD is classified into 3 levels of severity according to the internationally used definition of Jobe and Bancalari (1). FiO2 \>0.21 for ≥ 28 days and 1. Breathing room air (mild) 2. FiO2 \<0.3 (moderate) 3. FiO2 ≥ 0.3 and/or positive pressure support (severe) (1) Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723-9. |
| Oxygen saturation (SpO2) and fraction of inspired oxygen (FiO2) | 24 hours | The mean SpO2/FiO2 ratio within 24 hours of starting of intervention will be documented. |
| Frequency of any treatment failure | Individual study duration: estimated to be between a minimum of 7 days to an (estimated) maximum of 10 weeks. | Treatment failure is a composite outcome (see Outcome 1). The frequency of any treatment failure during the duration of the study will be documented. |
| Rescue NCPAP | Individual study duration: estimated to be between 7 days to 10 weeks. | Rescue NCPAP is defined as NCPAP \>6 cm H2O. The frequency of need for Rescue NCPAP during the duration of the study will be collected. |
| Postmenstrual age (PMA) off positive pressure support | Estimated to be at a PMA of approximately 29 to 34 weeks. | The investigators will document the PMA when the infant is off positive pressure support. |
| Postmenstrual age (PMA) off FiO2 > 0.21 | Estimated to be at a PMA between approximately 28 to 34 weeks. | The investigators will document the PMA when the infant is off FiO2 \> 0.21 |
| Postmenstrual age (PMA) at discharge | Estimated to be at a PMA of approximately 38-40 weeks. | The investigators will document the PMA when the infant is being discharged from the hospital. |
| Cerebral oxygen saturation (cRSO2) 1 hour before until 3 hours after start of the intervention | 4 hours | The cerebral oxygen saturation (cRSO2) in \[%\] 1 hour before until 3 hours after start of the intervention will be measured by using Near-infrared spectroscopy (NIRS). |
| Time spent <55% cRSO2 1 hour before until 3 hours after start of the intervention | 4 hours | The time spent \<55% cRSO2 in \[min\] 1 hour before until 3 hours after start of the intervention will be measured by using Near-infrared spectroscopy (NIRS). |
| Cerebral oxygen saturation (cRSO2) 1 hour before until 3 hours after cessation of the intervention | 4 hours | The cerebral oxygen saturation (cRSO2) in \[%\] 1 hour before until 3 hours after cessation of the intervention will be measured by using Near-infrared spectroscopy (NIRS). |
| Time spent <55% cRSO2 1 hour before until 3 hours after cessation of the intervention | 4 hours | The time spent \<55% cRSO2 in \[min\] 1 hour before until 3 hours after cessation of the intervention will be measured by using Near-infrared spectroscopy (NIRS). |
| Change in end-expiratory lung impedance (ΔEELI) | 48 hours | The change Δ in end-expiratory lung impedance (ΔEELI) will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: * within 30 minutes before starting of intervention (baseline measurement) * 3 minutes before until 3 minutes after starting of intervention * within 30 minutes after starting of intervention * 2, 6, 12, 24, 36, and 48 hours after starting of intervention |
| Respiratory rate (RR) | 24 hours | The mean RR within 24 hours of starting of intervention will be documented. |
| Change in variability of tidal volume (ΔTV) | 48 hours | The change Δ in variability of tidal volume (ΔTV) will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: * within 30 minutes before starting of intervention (baseline measurement) * 3 minutes before until 3 minutes after starting of intervention * within 30 minutes after starting of intervention * 2, 6, 12, 24, 36, and 48 hours after starting of intervention |
| Change in ratio of tidal volume anterior/posterior (ΔRatio TV ap) | 48 hours | The change Δ in ratio of tidal volume anterior/posterior (ΔRatio TV ap) will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: * within 30 minutes before starting of intervention (baseline measurement) * 3 minutes before until 3 minutes after starting of intervention * within 30 minutes after starting of intervention * 2, 6, 12, 24, 36, and 48 hours after starting of intervention |
| Urinary cortisol | 24 hours | A 24-hour-urine-sample will be collected on the third study day. The urinary production rates of cortisol and the most important metabolites will be documented as an indicator for infant stress. |
| COMFORTneo score | 72 hours | The COMFORTneo score will be documented on the third, fourth and fifth study day. The score measures comfort and chronic pain by observation. |
| Revised Bernese Pain Scale for Neonates (BSN-R) score | 72 hours | The BSN-R score will be documented on the third, fourth and fifth study day. The score measures pain. |
| Parental assessment of comfort | 72 hours | The parents will be asked 3 predefined questions concerning their infants' comfort on the on the third, fourth and fifth study day. |
| NASA Task Load Index (NASA-TLX) | 72 hours | The NASA-TLX will be filled out by the participants' nurses on the third, fourth and fifth study day. The NASA-TLX is a questionnaire that measures workload. |
| Nasal trauma score | Individual study duration: estimated to be between 7 days to 10 weeks. | The nasal trauma score is assessed according to internal standard guidelines in case of a present nasal trauma. The highest respective score and time of assessment will be documented on the participant CRF at 36 weeks PMA. Measuring nasal trauma using the Nasal trauma score takes approximately 20 seconds. |
| Behavioral Sleep stage classification for Preterm Infants (BeSSPI) | 24 hours | Sleep-wake cycles as determined by the BeSSPI on the fourth study day will be documented. The BeSSPI identifies sleep stages by observation and takes approximately 2.5 hours. |
| Parental Bonding Questionnaire (PBQ) | At 36 weeks PMA | The score of the PBQ will be documented at 36 weeks PMA. The PBQ investigates infant-parental bonding. |
| Age at initiating breastfeeds | Estimated to be between 30-34 weeks PMA. | The postmenstrual age (PMA) at initiating breastfeeds will be documented. This refers to the PMA at which the first successful breastfeeding attempt takes place. |
| Age at reaching full breastfeeds | Estimated to be between 34-40 weeks PMA. | The postmenstrual age (PMA) at reaching full breastfeeds will be documented. This corresponds to 100% nutrition per breastfeeds for 24 consecutive hours. |
| Weight | At 36 weeks PMA | The weight in \[g\] at 36 weeks postmenstrual age (PMA) will be documented. |
| Head circumference | At 36 weeks PMA | The head circumference in \[cm\] at 36 weeks postmenstrual age (PMA) will be documented. |
| Change in global inhomogeneity (ΔGI) index | 48 hours | The change Δ in global inhomogeneity (ΔGI) index will be measured using electrical impedance tomography (EIT) at 9 different timepoints during the first 48 hours after starting of intervention. One measurement will last 6 minutes. The measurements will take place: * within 30 minutes before starting of intervention (baseline measurement) * 3 minutes before until 3 minutes after starting of intervention * within 30 minutes after starting of intervention * 2, 6, 12, 24, 36, and 48 hours after starting of intervention |
Countries
Germany, Switzerland
Contacts
Primary ContactLisa Marie Bünte
Backup ContactAndré Kidszun, Prof. Dr. med.
Outcome results
None listed