Premature NeonateHYFIVENCT02799875
Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants
A study testing Higher permissive hypercapnia and Lower Permissive Hypercapnia in people with Premature Neonate, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 to 14 days
- Conditions the study is for
- Premature Neonate
- What is being tested?
- Higher permissive hypercapnia and Lower Permissive Hypercapnia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Apr 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- Major malformation
- Neuromuscular condition that affects respiration
- Terminal illness
- Attending physician has made a decision to withhold or limit support for the infant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Premature Neonate
- Being tested
- Higher permissive hypercapnia, Lower Permissive Hypercapnia
- Keywords
- respiratory distress syndrome, permissive hypercapnia, ventilator strategy
- Medical subject headings
- Premature Birth, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Higher permissive hypercapniaOther
- pCO2 ≥ 60mmHg with an upper limit ≤ 75mmHg;
- pH ≥ 7.20 from a capillary or arterial blood sample;
Lower Permissive HypercapniaOther
- pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg;
- pH ≥ 7.25 from a capillary or arterial blood sample;
| Study group | Role | What they receive |
|---|---|---|
| Higher permissive hypercapnia | Active comparator | 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. Receives: Other: Higher permissive hypercapnia |
| Lower permissive hypercapnia | Active comparator | 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. Receives: Other: Lower Permissive Hypercapnia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alive Ventilator-free Days from Randomization to 28 Days after randomization
Number of days from time of randomization through 28 days after randomization
Measured: From randomization until 28 days after randomization
Secondary outcomes (10)
All Causes of Death
All causes of death between randomization and anticipated 120 days after birth
Measured: Randomization to 120 days after birth
Incidence of bronchopulmonary dysplasia "BPD"
Defined as need for supplemental oxygen per physiologic definition
Measured: Measured at 36 weeks postmenstrual age
Open label treatment with postnatal steroids for bronchopulmonary dysplasia
Any treatment with postnatal steroids for bronchopulmonary dysplasia
Measured: 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
Measured: 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
Measured: Randomization to 28 days post randomization
Neurodevelopmental Impairment
Results of Bayley Scales of Development, Version III
Measured: Measured at 22-26 months corrected gestational age
Growth Indices-Weight
Weekly weights taken per clinical standard
Measured: Randomization to 28 days post randomization
Growth Indices-Head Circumference
Weekly head circumferences taken per clinical standard
Measured: Randomization to 28 days post randomization
Pulmonary Hypertension
Documentation of presence of pulmonary hypertension by echocardiogram
Measured: 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
Measured: On routine head ultrasound closest to 28 days after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2016 (estimated)
- Study startDec 2015
- Primary completionApr 2021
- Study completionApr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Premature NeonateStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Colm Travers, University of Alabama at Birmingham
- Investigators
- Colm P Travers, MB BCh BAo, Principal investigator, University of Alabama at BirminghamWaldemar A Carlo, MD, Study director, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02799875
- Sponsor's protocol ID
- UAB Neo 014
- Acronym
- HYFIVE
- Status last verified
- Apr 2021
- First submitted
- 10 May 2016
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Travers CP, Gentle SJ, Shukla VV, Aban I, Yee AJ, Armstead KM, Benz RL, Laney D, Ambalavanan N, Carlo WA. Late Permissive Hypercapnia for Mechanically Ventilated Preterm Infants: A Randomized Trial. Pediatr Pulmonol. 2025 Jun;60(6):e71165. doi: 10.1002/ppul.71165.
PubMed 40525736
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of pH-Controlled Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants
- ClinicalTrials.gov ID
- NCT02799875
- Acronym / sponsor ID
- HYFIVE / UAB Neo 014
- Conditions
- Premature Neonate
- Keywords
- respiratory distress syndrome, permissive hypercapnia, ventilator strategy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- Apr 2021 (actual)
- Study completion
- Apr 2021 (actual)
- First posted
- 15 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Higher permissive hypercapnia | Active comparator | Other: Higher permissive hypercapniaExtubation 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 | Active comparator | Other: Lower Permissive HypercapniaExtubation 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. |
Who may qualify
- Ages
- 7 to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (4 listed)
- Major malformation
- Neuromuscular condition that affects respiration
- Terminal illness
- Attending physician has made a decision to withhold or limit support for the infant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Higher permissive hypercapnia* pCO2 ≥ 60mmHg with an upper limit ≤ 75mmHg; * pH ≥ 7.20 from a capillary or arterial blood sample; | Other | Higher permissive hypercapnia |
| Lower Permissive Hypercapnia* pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg; * pH ≥ 7.25 from a capillary or arterial blood sample; | Other | Lower permissive hypercapnia |
Primary outcome
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
10 secondary outcomes
All Causes of Death
Time frame: Randomization to 120 days after birth
Incidence of bronchopulmonary dysplasia "BPD"
Time frame: Measured at 36 weeks postmenstrual age
Open label treatment with postnatal steroids for bronchopulmonary dysplasia
Time frame: Randomization to 120 days after birth
Number of days alive, Continuous Positive Airway Pressure (CPAP)-free
Time frame: Randomization to 28 days post randomization
Number of days alive, supplemental oxygen free
Time frame: Randomization to 28 days post randomization
Neurodevelopmental Impairment
Time frame: Measured at 22-26 months corrected gestational age
Growth Indices-Weight
Time frame: Randomization to 28 days post randomization
Growth Indices-Head Circumference
Time frame: Randomization to 28 days post randomization
Pulmonary Hypertension
Time frame: Routine echocardiogram performed at 28+/- 7 days after birth
Intracranial Hemorrhage
Time frame: On routine head ultrasound closest to 28 days after birth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Derived from this study: PubMed 40525736Travers CP, Gentle SJ, Shukla VV, Aban I, Yee AJ, Armstead KM, Benz RL, Laney D, Ambalavanan N, Carlo WA. Late Permissive Hypercapnia for Mechanically Ventilated Preterm Infants: A Randomized Trial. Pediatr Pulmonol. 2025 Jun;60(6):e71165. doi: 10.1002/ppul.71165.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colm P Travers, MB BCh BAo principal investigator
University of Alabama at Birmingham
Waldemar A Carlo, MD study director
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Higher permissive hypercapnia and Lower Permissive Hypercapnia in people with Premature Neonate, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alive Ventilator-free Days from Randomization to 28 Days after randomization (time frame: From randomization until 28 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02799875, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.