A Randomized Controlled Trial of pH-Controlled Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- Alive Ventilator-free Days from Randomization to 28 Days after randomization
Study Overview
Brief Summary
Preterm infants, less than 37 weeks gestation with respiratory distress syndrome, who remain ventilated between 7 and 14 days after birth will be randomized to a ventilator strategy of either a higher level of permissive hypercapnia or of a lower level of permissive hypercapnia to determine if either strategy will increase the number of alive ventilator-free days in the 28 days after randomization.
Detailed Description
22.0 to 36.6 weeks gestational age preterm infants with respiratory distress syndrome, who remain ventilated between 7 and 14 days after birth will be randomized to one of two ventilator strategies: 1) a higher level of permissive hypercapnia or 2) a lower level of permissive hypercapnia to determine if either strategy will increase the number of alive ventilator-free days in the 28 days after randomization.
After parental consent obtained, intubated, mechanically ventilated infants will be randomized by use of sequentially numbered sealed opaque envelopes to the treatment assignment. Randomized infants will be stratified by gestational age at delivery (< 26 weeks, ≥ 26 wks but less than 29 weeks, and ≥ 29 weeks). Multiple births will be randomized to the same group. The envelope will be opened only on days 7-14 when infant meets criteria. Clinicians will follow pre-specified algorithms of extubation and reintubation criteria to wean infants from mechanical ventilation. The ventilation algorithms may be set aside until the infant is deemed stable enough to allow resumption of the study algorithm.
Infant will be extubated within 24 hours of meeting extubation criteria and documented on a single blood gas. A trial of extubation per attending physician is allowed independent of the trial protocol.All other care is per unit standard.
Reports of routine follow-up after discharge in babies < 27 weeks gestation will be obtained to determine neurodevelopmental impairment on this subset of babies.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 7 Days to 14 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Gestational age at least 22 but less than 37 weeks;
- •Intubated on mechanical ventilation for respiratory distress syndrome on days 7-14 after birth;
- •Admitted to Neonatal Intensive Care Unit before 7 days after birth;
- •Informed consent per parent(s)
Exclusion Criteria
- •Major malformation
- •Neuromuscular condition that affects respiration
- •Terminal illness
- •Attending physician has made a decision to withhold or limit support for the infant
Arms & Interventions
Higher permissive hypercapnia
Extubation criteria: partial pressure carbon dioxide (pCO2) ≥ 60mmHg with an upper limit ≤ 75mmHg; pH ≥ 7.20; oxygen saturation (SpO2) ≥ 88% with fraction of inspired oxygen (FiO2) ≤ 0.50; mean airway pressure (MAP) < 8 cm H2O, ventilator rate ≤ 20 bpm, amplitude < 2X MAP if on high frequency ventilation (HFV); hemodynamically stable (clinically acceptable blood pressure and perfusion per clinical team opinion). In addition, reintubation may occur if any of the following are met: PCO2 > 75mmHg; pH < 7.20; FiO2 ≥0.80 required to maintain SpO2 ≥ 88% for one hour; hemodynamic instability; clinically defined shock; repetitive apnea (> 1 episode per hour) requiring bag and mask ventilation; sepsis; and/or need for surgery.
Intervention: Higher permissive hypercapnia (Other)
Lower permissive hypercapnia
Extubation criteria: pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg; pH ≥ 7.25; SpO2 ≥ 88% with FiO2 ≤ 0.50; mean airway pressure (MAP) < 8 cm H2O, ventilator rate ≤ 20 bpm, amplitude < 2X MAP if on high frequency ventilation (HFV); hemodynamically stable (clinically acceptable blood pressure and perfusion per clinical team opinion). In addition, reintubation may occur if any of the following are met: PCO2 > 55mmHg; pH < 7.25; FiO2 ≥0.80 required to maintain SpO2 ≥ 88% for one hour; hemodynamic instability; clinically defined shock; repetitive apnea (> 1 episode per hour) requiring bag and mask ventilation; sepsis; and/or need for surgery.
Intervention: Lower Permissive Hypercapnia (Other)
Outcomes
Primary Outcomes
Alive Ventilator-free Days from Randomization to 28 Days after randomization
Time Frame: From randomization until 28 days after randomization
Number of days from time of randomization through 28 days after randomization
Secondary Outcomes
- Neurodevelopmental Impairment(Measured at 22-26 months corrected gestational age)
- Open label treatment with postnatal steroids for bronchopulmonary dysplasia(Randomization to 120 days after birth)
- Growth Indices-Weight(Randomization to 28 days post randomization)
- Number of days alive, Continuous Positive Airway Pressure (CPAP)-free(Randomization to 28 days post randomization)
- All Causes of Death(Randomization to 120 days after birth)
- Number of days alive, supplemental oxygen free(Randomization to 28 days post randomization)
- Incidence of bronchopulmonary dysplasia "BPD"(Measured at 36 weeks postmenstrual age)
- Growth Indices-Head Circumference(Randomization to 28 days post randomization)
- Pulmonary Hypertension(Routine echocardiogram performed at 28+/- 7 days after birth)
- Intracranial Hemorrhage(On routine head ultrasound closest to 28 days after birth)
Investigators
Colm Travers
Principal Investigator
University of Alabama at Birmingham