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

A Randomized Controlled Trial of pH-Controlled Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants

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.

Study Overview

• Status: Completed
• Conditions: Premature Neonate
• Intervention / Treatment: Other: Higher permissive hypercapnia; Other: Lower Permissive Hypercapnia

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 Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • UAB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Other: Higher permissive hypercapnia; pCO2 ≥ 60mmHg with an upper limit ≤ 75mmHg;; pH ≥ 7.20 from a capillary or arterial blood sample;
Active Comparator: 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.	Other: Lower Permissive Hypercapnia; pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg;; pH ≥ 7.25 from a capillary or arterial blood sample;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alive Ventilator-free Days from Randomization to 28 Days after randomization	Number of days from time of randomization through 28 days after randomization	From randomization until 28 days after randomization

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Colm P Travers, MB BCh BAO, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: May 10, 2016
• First Submitted That Met QC Criteria: June 11, 2016
• First Posted (Estimate): June 15, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: respiratory distress syndrome; permissive hypercapnia; ventilator strategy
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Hypercapnia
• Other Study ID Numbers: UAB Neo 014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No