Late Permissive Hypercapnia for Intubated and Ventilated Preterm Infants

NCT ID: NCT02799875

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-04-30

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.

Conditions

Premature Neonate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Higher permissive hypercapnia

Intervention Type: OTHER

• pCO2 ≥ 60mmHg with an upper limit ≤ 75mmHg;
• pH ≥ 7.20 from a capillary or arterial blood sample;

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.

Group Type: ACTIVE_COMPARATOR

Lower Permissive Hypercapnia

Intervention Type: OTHER

• pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg;
• pH ≥ 7.25 from a capillary or arterial blood sample;

Interventions

Higher permissive hypercapnia

• pCO2 ≥ 60mmHg with an upper limit ≤ 75mmHg;
• pH ≥ 7.20 from a capillary or arterial blood sample;

Intervention Type: OTHER

Lower Permissive Hypercapnia

• pCO2 ≥ 40mmHg with an upper limit ≤ 55mmHg;
• pH ≥ 7.25 from a capillary or arterial blood sample;

Intervention Type: OTHER

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

• Minimum Eligible Age: 7 Days
• Maximum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Colm Travers

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Colm P Travers, MB BCh BAo

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Waldemar A Carlo, MD

Role: STUDY_DIRECTOR

University of Alabama at Birmingham

Locations

UAB

Birmingham, Alabama, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40525736 (View on PubMed)

Other Identifiers

UAB Neo 014

Identifier Type: -

Identifier Source: org_study_id