Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants

Not Applicable

Completed

• Conditions: Premature Neonate
• Interventions: Other: Higher permissive hypercapnia; Other: Lower Permissive Hypercapnia

• Registration Number: NCT02799875
• Lead Sponsor: University of Alabama at Birmingham

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 Timeline

• Study Start: 2015-12
• Study First Submitted: 2016-05-10
• Study First Submitted QC: 2016-06-11
• Study First Posted: 2016-06-15
• Status Verified: 2021-04
• Primary Completion: 2021-04
• Study Completion: 2021-04
• Last Update Submitted: 2021-04-28
• Last Update Posted: 2021-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Higher permissive hypercapnia	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.
Lower permissive hypercapnia	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.

Primary Outcome Measures

Name	Time	Method
Alive Ventilator-free Days from Randomization to 28 Days after randomization	From randomization until 28 days after randomization	Number of days from time of randomization through 28 days after randomization

Secondary Outcome Measures

Name	Time	Method
Neurodevelopmental Impairment	Measured at 22-26 months corrected gestational age	Results of Bayley Scales of Development, Version III
Open label treatment with postnatal steroids for bronchopulmonary dysplasia	Randomization to 120 days after birth	Any treatment with postnatal steroids for bronchopulmonary dysplasia
Growth Indices-Weight	Randomization to 28 days post randomization	Weekly weights taken per clinical standard
Number of days alive, Continuous Positive Airway Pressure (CPAP)-free	Randomization to 28 days post randomization	Number of days alive, not receiving CPAP from randomization to 28 days post randomization
All Causes of Death	Randomization to 120 days after birth	All causes of death between randomization and anticipated 120 days after birth
Number of days alive, supplemental oxygen free	Randomization to 28 days post randomization	Number of days alive, not receiving oxygen from randomization to 28 days post randomization
Incidence of bronchopulmonary dysplasia "BPD"	Measured at 36 weeks postmenstrual age	Defined as need for supplemental oxygen per physiologic definition
Growth Indices-Head Circumference	Randomization to 28 days post randomization	Weekly head circumferences taken per clinical standard
Pulmonary Hypertension	Routine echocardiogram performed at 28+/- 7 days after birth	Documentation of presence of pulmonary hypertension by echocardiogram
Intracranial Hemorrhage	On routine head ultrasound closest to 28 days after birth	Evidence of new or increased intracranial hemorrhage as documented on clinically obtained cranial ultrasounds closest to day 28 after birth

Trial Locations

Locations (1)

UAB; 🇺🇸 Birmingham, Alabama, United States