Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants (HYFIVE)

The University of Alabama at Birmingham

Status: Completed

Conditions: Premature Neonate

Treatments: Other: Higher permissive hypercapnia; Other: Lower Permissive Hypercapnia

Study type: Interventional

Funder types: Other

Identifiers

NCT02799875

UAB Neo 014

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 patients

Sex: All

Ages: 7 to 14 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

Higher permissive hypercapnia

Active Comparator group

Description:

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.

Treatment:

Other: Higher permissive hypercapnia

Lower permissive hypercapnia

Active Comparator group

Description:

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.

Treatment:

Other: Lower Permissive Hypercapnia