BronchoPulmonary Dysplasia, Extremely Low Birth Weight Infant (ELBW), Neonatal Respiratory Distress Syndrome
Conditions
Keywords
CPAP, Extremely Low Birth Weight Infant (ELBW), Non-invasive respiratory support, Premature infants, Non invasive ventilation weaning
Brief summary
Though Nasal Continuous Positive Airway Pressure (NCPAP) is a commonly used form of non-invasive neonatal respiratory support, the optimal method of weaning off NCPAP is not well established. In this prospective, two-center randomized control trial we hypothesize that gradually increasing time off NCPAP (sprinting) increases the success of weaning NCPAP off in infants born between 23 0/7-30 6/7 weeks of gestational age.
Detailed description
Eligible infants admitted to two Neonatal Intensive Care Units (NICUs) were randomized to a sprinting (SP) vs. a non-sprinting (NSP) protocol, both over 4 days. Infants assigned to the SP group sprinted twice daily for 3h (day 1), 6h (day 2), 9h (day 3) & then 24h back on NCPAP (day 4) before switching to nasal cannula (NC) on day 5. Infants in the NSP group were maintained on NCPAP of 5 cm of water for the first 4 days before switching to NC on day 5, similar to the SP group. Infants in both groups were observed for the next 3 days (day 5-7) to ensure stability off CPAP
Interventions
DEVICENCPAP
Nasal Continuous Positive Airway Pressure
Sponsors
Children's Hospital of Orange County
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
26 Weeks to No maximum
Healthy volunteers
No
Inclusion criteria
* Born between 23 0/7 - 30 6/7 weeks GA * At least 26 0/7 weeks corrected GA. * On NCPAP for at least 24 hours * Stable on ≤0.3 FiO2 for at least 24 hours Initiation of study protocol, i.e., weaning from NCPAP, was started when infant met all of the following criteria for at least 24 hours: * Requiring NCPAP of 4-6 cm of H2O and FiO2 ≤0.3. * All babies \< 32 weeks corrected GA should have been loaded or already on maintenance caffeine (caffeine citrate 20 mg/kg as the loading and 5-10 mg/kg as the maintenance dose). * Stable respiratory system assessment (respiratory rate of \< 70/min, no significant chest retractions (sternal/ diaphragmatic), and baseline oxygen saturation \> 86%) and otherwise deemed clinically stable for weaning off non-invasive ventilation by medical team * If post-surgery, infant must be at least 2 weeks post-operative and off antibiotics with no concern or need for repeat surgery. * A documented hemoglobin of more than 8 g/dl within 7 days of initiation of the study. * Meeting stability criteria defined below: * The infant had to be tolerating a flow of no more than 2 liters NC on a FiO2 of 0.30 or less to keep oxygen saturations above 85% (should match what you wrote below in failure criteria)%. * Have a respiratory rate of less than 70 on average over 24 hours for more than 24 hours * The infant could have no significant chest recession (sternal/diaphragmatic)
Exclusion criteria
* Evidence of a hemodynamically or clinically significant (worsening respiratory status or pulmonary edema on chest x-ray) Patent ductus arteriosus, diagnosed either clinically or echocardiographically. * Any significant congenital abnormality (abnormalities affecting a major organ system, airway, or musculoskeletal system). * Hemodynamic/respiratory instability or currently being treated for suspected or proven sepsis (positive blood culture) * Grade IV intraventricular hemorrhage * Inability to obtain informed parental consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Wean Off CPAP at the First Attempt | 7 days | Measured by successful wean off CPAP on first attempt, i.e., no NCPAP requirement after 7 days on wean protocol on first attempt. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Retinopathy of Prematurity (ROP) | 1-2 months | Measured as clinical signs of stage 2 or above ROP on retinal exam prior to discharge |
| Number of Participants With Periventricular Leukomalacia (PVL) | 1-2 months | Measured as radiologic findings of PVL noted prior to discharge |
| Length of Stay (Days) | 60-108 days | Measures as the number of days patient remained hospitalized after birth at the study hospital. |
| Number of Participants With Bronchopulmonary Dysplasia | 1-2 months | Measured as an oxygen requirement at 36 weeks corrected gestational age |
| Number of Attempts to Wean Off CPAP | Until completely weaned off CPAP | Number of attempts made to wean off CPAP |
| Number of Days on Protocol | 7-10 days | Measured as the total number of days the patient was on the study protocol |
| Corrected Gestational Age at Time of Discharge/Transfer | 36weeks-41weeks | Measured as the corrected gestational age at which the patient was discharged or transferred. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sprinting Take off NCPAP twice daily for 3hours (day 1), Take off NCPAP twice daily for 6hours (day 2), Take off NCPAP twice daily for 9hours (day 3), Placed back on NCPAP for 24hours (day 4), Switch to nasal cannula at a flow rate of 1.5-2 L/min (day 5)
NCPAP: Nasal Continuous Positive Airway Pressure | 40 |
| Non-Sprinting * If the infant was on NCPAP 6, Infant was weaned down to CPAP 5 for 96 hours. If they met stability criteria, then infant was switched to room air (no flow) or no more than 2L NC.
* If the infant was on NCPAP 5, the infant was continued on CPAP 5 for 96 hours If they met stability criteria, then infant was switched to room air (no flow) or no more than 2L NC.
NCPAP: Nasal Continuous Positive Airway Pressure | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Sprinting | Non-Sprinting | Total |
|---|---|---|---|
| Age, Continuous | 33.4 Weeks | 33.2 Weeks | 33.3 Weeks |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 21 Participants | 25 Participants | 46 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Number of Participants With Successful Wean Off CPAP at the First Attempt
Measured by successful wean off CPAP on first attempt, i.e., no NCPAP requirement after 7 days on wean protocol on first attempt.
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sprinting | Number of Participants With Successful Wean Off CPAP at the First Attempt | 31 Participants |
| Non-Sprinting | Number of Participants With Successful Wean Off CPAP at the First Attempt | 30 Participants |
Secondary
Corrected Gestational Age at Time of Discharge/Transfer
Measured as the corrected gestational age at which the patient was discharged or transferred.
Time frame: 36weeks-41weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sprinting | Corrected Gestational Age at Time of Discharge/Transfer | 33.4 weeks |
| Non-Sprinting | Corrected Gestational Age at Time of Discharge/Transfer | 33.2 weeks |
Secondary
Length of Stay (Days)
Measures as the number of days patient remained hospitalized after birth at the study hospital.
Time frame: 60-108 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sprinting | Length of Stay (Days) | 82.5 Days |
| Non-Sprinting | Length of Stay (Days) | 78 Days |
Secondary
Number of Attempts to Wean Off CPAP
Number of attempts made to wean off CPAP
Time frame: Until completely weaned off CPAP
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sprinting | Number of Attempts to Wean Off CPAP | 1 Attempt |
| Non-Sprinting | Number of Attempts to Wean Off CPAP | 1 Attempt |
Secondary
Number of Days on Protocol
Measured as the total number of days the patient was on the study protocol
Time frame: 7-10 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sprinting | Number of Days on Protocol | 7 Days |
| Non-Sprinting | Number of Days on Protocol | 7 Days |
Secondary
Number of Participants With Bronchopulmonary Dysplasia
Measured as an oxygen requirement at 36 weeks corrected gestational age
Time frame: 1-2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sprinting | Number of Participants With Bronchopulmonary Dysplasia | 11 Participants |
| Non-Sprinting | Number of Participants With Bronchopulmonary Dysplasia | 14 Participants |
Secondary
Number of Participants With Periventricular Leukomalacia (PVL)
Measured as radiologic findings of PVL noted prior to discharge
Time frame: 1-2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sprinting | Number of Participants With Periventricular Leukomalacia (PVL) | 0 Participants |
| Non-Sprinting | Number of Participants With Periventricular Leukomalacia (PVL) | 1 Participants |
Secondary
Number of Participants With Retinopathy of Prematurity (ROP)
Measured as clinical signs of stage 2 or above ROP on retinal exam prior to discharge
Time frame: 1-2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sprinting | Number of Participants With Retinopathy of Prematurity (ROP) | 12 Participants |
| Non-Sprinting | Number of Participants With Retinopathy of Prematurity (ROP) | 15 Participants |