Bronchopulmonary Dysplasia (BPD)
Conditions
Keywords
Continuous Positive Airway Pressure, CPAP
Brief summary
The objective of the CPAP Trial is to test whether extending CPAP until 34 weeks' PMA or for at least 2 additional weeks compared to weaning to a nasal canula will decrease the likelihood of bronchopulmonary dysplasia or death at 36 weeks' PMA.
Interventions
DEVICECPAP
Prior to study entry, the CPAP interface (includes RAM cannula, Optiflow, large bore cannulas, mask, prongs) and mode (bubble, variable-flow, ventilator-derived) used is at the discretion of the provider and center. After study entry, CPAP will be provided via mask or binasal prongs to maintain a relatively uniform CPAP delivery system among infants in the treatment group. Bubble CPAP will be preferred over other modes of CPAP delivery whenever available.
DEVICENasal Cannula
HFNC at 4 L/min will be used initially in the control group. Flow should be titrated down by 1 L/min per day until ≤0.5 L/kg among infants in the nasal cannula group if not meeting pre-specified failure criteria to reduce the risk of inadvertent positive end-expiratory pressure (PEEP). Flow can also be increased (up to 6 L/min maximum) if needed among infants on NC who meet the pre-specified failure criteria. Infants in the control group placed back on CPAP may use an interface at provider discretion.
Sponsors
NICHD Neonatal Research Network
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
The inherent nature of ventilator/respiratory support interventions often precludes the ability to blind investigators and caregivers. As such, many studies in this domain face the limitation of not being blinded. The study team recognizes this limitation and will implement measures to mitigate potential biases arising from an unblinded trial. The DCC PI who will be overseeing the statistical team will be masked. Additionally, interim analysis (efficacy and safety) reports presented to the Data and Safety Monitoring Board (DSMB) will be masked.
Intervention model description
This will be a randomized controlled trial with a 1:1 parallel allocation of infants to Continuous Positive Airway Pressure (CPAP) or Nasal Cannula (NC) using stratified permuted block design. Randomization will be stratified by gestational age (≥ 22 0/7 weeks to ≤ 24 6/7 weeks, ≥ 25 0/7 weeks to ≤ 26 6/7, and ≥ 27 0/7 to ≤ 28 6/7).
Eligibility
Sex/Gender
ALL
Age
No minimum to 31 Weeks
Healthy volunteers
No
Inclusion criteria
* Gestational age \<29 weeks at birth * PMA \<32 weeks at study entry * On treatment with CPAP without a rate in FiO2 \<0.25 and PEEP of 4-5 cmH2O * Meet stability criteria: * If previously intubated must be extubated ≥ 72 hours * \<3 self-resolving apneas (≤ 20 s) and/or bradycardia (\<100 bpm) in any hour over previous 6 hours * No episodes of apnea or bradycardia requiring intervention (oxygen/stimulation/bag and mask) for 24 hours * Parents/legal guardians consent for enrollment
Exclusion criteria
* Major malformation * Neuromuscular condition that affects respiration * Terminal illness * Decision to withhold or limit support * Too sick to participate in opinion of Attending physician * Clinical shock, sepsis * Planned surgery during study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bronchopulmonary Dysplasia or Death | 36 Weeks' PMA | The likelihood of BPD or death at 36 weeks' Postmenstrual Age (PMA): a five-level ordinal outcome (death, survival with grade 3 BPD, survival with grade 2 BPD, survival with grade 1 BPD, and survival free of any BPD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days alive and off respiratory support | 34-40 weeks' PMA | The number of days alive and off respiratory support from 34 weeks' to 40 weeks' PMA |
| Mortality at 36 Weeks | 36 Weeks' PMA | Mortality |
| Death or Grade 2-3 BPD | 36 Weeks' PMA | Mortality at 36 weeks' PMA or grade 3 BPD |
| Death or Grade 3 BPD | 36 Weeks' PMA | Mortality or grade 3 BPD |
| Retinopathy of prematurity | 52 weeks' PMA | Retinopathy of prematurity ≥ stage 3 or requiring treatment (laser/anti-VEGF) |
| Respiratory support, supplemental oxygen, and pulmonary medications | 40 weeks' PMA | Use of supplemental oxygen, respiratory support (including low-flow nasal cannula), and pulmonary medications (methylxanthines, steroids, diuretics, albuterol) at discharge and 40 weeks' PMA |
| Full PO feedings | 52 weeks' PMA | PMA at first full PO feeding (where full PO feeding is defined as intake of 120 mL/kg/day by mouth, even if an NG tube remains in situ) |
| Length of hospitalization | 52 Weeks' PMA | Length of hospitalization from 34 weeks' PMA |
Outcome results
None listed