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

Primary Purpose

Premature Neonate

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Higher permissive hypercapnia
Lower Permissive Hypercapnia
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Premature Neonate focused on measuring respiratory distress syndrome, permissive hypercapnia, ventilator strategy

Eligibility Criteria

7 Days - 14 Days (Child)All SexesDoes not accept 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

Sites / Locations

  • UAB

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Higher permissive hypercapnia

Lower permissive hypercapnia

Arm 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.

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.

Outcomes

Primary Outcome Measures

Alive Ventilator-free Days from Randomization to 28 Days after randomization
Number of days from time of randomization through 28 days after randomization

Secondary Outcome Measures

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

Full Information

First Posted
May 10, 2016
Last Updated
April 28, 2021
Sponsor
University of Alabama at Birmingham
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1. Study Identification

Unique Protocol Identification Number
NCT02799875
Brief Title
Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants
Acronym
HYFIVE
Official Title
A Randomized Controlled Trial of pH-Controlled Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
December 2015 (undefined)
Primary Completion Date
April 2021 (Actual)
Study Completion Date
April 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Premature Neonate
Keywords
respiratory distress syndrome, permissive hypercapnia, ventilator strategy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Higher permissive hypercapnia
Arm Type
Active Comparator
Arm 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.
Arm Title
Lower permissive hypercapnia
Arm Type
Active Comparator
Arm 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.
Intervention Type
Other
Intervention Name(s)
Higher permissive hypercapnia
Intervention Description
pCO2 ≥ 60mmHg with an upper limit ≤ 75mmHg; pH ≥ 7.20 from a capillary or arterial blood sample;
Intervention Type
Other
Intervention Name(s)
Lower Permissive Hypercapnia
Intervention Description
pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg; pH ≥ 7.25 from a capillary or arterial blood sample;
Primary Outcome Measure Information:
Title
Alive Ventilator-free Days from Randomization to 28 Days after randomization
Description
Number of days from time of randomization through 28 days after randomization
Time Frame
From randomization until 28 days after randomization
Secondary Outcome Measure Information:
Title
All Causes of Death
Description
All causes of death between randomization and anticipated 120 days after birth
Time Frame
Randomization to 120 days after birth
Title
Incidence of bronchopulmonary dysplasia "BPD"
Description
Defined as need for supplemental oxygen per physiologic definition
Time Frame
Measured at 36 weeks postmenstrual age
Title
Open label treatment with postnatal steroids for bronchopulmonary dysplasia
Description
Any treatment with postnatal steroids for bronchopulmonary dysplasia
Time Frame
Randomization to 120 days after birth
Title
Number of days alive, Continuous Positive Airway Pressure (CPAP)-free
Description
Number of days alive, not receiving CPAP from randomization to 28 days post randomization
Time Frame
Randomization to 28 days post randomization
Title
Number of days alive, supplemental oxygen free
Description
Number of days alive, not receiving oxygen from randomization to 28 days post randomization
Time Frame
Randomization to 28 days post randomization
Title
Neurodevelopmental Impairment
Description
Results of Bayley Scales of Development, Version III
Time Frame
Measured at 22-26 months corrected gestational age
Title
Growth Indices-Weight
Description
Weekly weights taken per clinical standard
Time Frame
Randomization to 28 days post randomization
Title
Growth Indices-Head Circumference
Description
Weekly head circumferences taken per clinical standard
Time Frame
Randomization to 28 days post randomization
Title
Pulmonary Hypertension
Description
Documentation of presence of pulmonary hypertension by echocardiogram
Time Frame
Routine echocardiogram performed at 28+/- 7 days after birth
Title
Intracranial Hemorrhage
Description
Evidence of new or increased intracranial hemorrhage as documented on clinically obtained cranial ultrasounds closest to day 28 after birth
Time Frame
On routine head ultrasound closest to 28 days after birth

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Days
Maximum Age & Unit of Time
14 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colm P Travers, MB BCh BAo
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Waldemar A Carlo, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Study Director
Facility Information:
Facility Name
UAB
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants

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