Oxygenation Instability and Maturation of Control of Breathing in Premature Infants

Infant,Premature Clinical Trial

Official title:

Oxygenation Instability and Maturation of Control of Breathing in Premature Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03445689
• Other study ID #: 20161114
• Secondary ID: U01HL133689
• Status: Completed
• Start date: September 4, 2018
• Est. completion date: November 1, 2023

Study information

• Verified date: November 2023
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. These infants are also exposed to hyperoxemia. The objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system. This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

Description:

Most extreme premature infants present with respiratory failure due to altered lung function compounded by breathing instability due to an immature respiratory control function. Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. As a result, these infants receive oxygen supplementation but this is often excessive and these infants are also exposed to hyperoxemia. The extent to which these episodes of hypoxemia or the exposure to hyperoxemia impact on the maturation and function of the control of breathing system in extreme premature infants during the evolving stages of their respiratory disease is unknown. This is a prospective study that will systematically evaluate such association in extreme premature infants. The main objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system. This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: November 1, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Premature infants born at 23 0/7- 28 6/7 weeks gestational age
• Postnatal age up to equivalent to 36 weeks postmenstrual age
• Requiring supplemental oxygen and/or receiving mechanical ventilation, CPAP, nasal ventilation or nasal cannula

Exclusion Criteria:

• Severe congenital anomalies that may affect life expectancy or pulmonary or neurosensory development
• Severe CNS pathology that may alter respiratory control function

Related Conditions & MeSH terms

• Infant,Premature
• Premature Birth

Intervention

Other:
• Assessment of oxygenation instability
Recordings of SpO2 and heart rate will be analyzed by dedicated software to obtain frequency, duration and severity of episodes of hypoxemia and hyperoxemia.
• Determination of mechanisms of hypoxemia episodes
Recordings of SpO2, heart rate, esophageal pressure, tidal volume, minute volume, respiratory rate and transcutaneous PCO2 will be analyzed to determine the prevalence, severity and duration of hypoxemia episodes produced by the different mechanisms.
• Assessment of respiratory instability
Recordings of tidal volume, minute volume and respiratory rate will be analyzed to determine frequency of apnea, periodic breathing, distribution of inter-breath intervals.
• apneic threshold of CO2
In mechanically ventilated infants the apneic threshold of CO2 will be measured by transcutaneous PCO2 following a step wise increase in ventilator rate until spontaneous breathing ceases transiently. In spontaneously breathing infants the apnea threshold of CO2 will be measured during episodes central apnea.
• Assessment of peripheral chemoreceptor function
The Dejours test will be used to assess peripheral chemoreceptor function by measuring the immediate ventilatory response to high-inspired oxygen.
• Assessment of central chemo-receptor function
Central chemo-receptor function will be assessed by measuring the ventilatory response to inspired CO2.

Locations

Country	Name	City	State
United States	NICU at Holtz Children's Hospital	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peripheral chemoreceptor control of breathing function	Ventilatory response to oxygen (Dejours test)	at 32 weeks corrected postmenstrual age
Primary	Peripheral chemoreceptor control of breathing function	Ventilatory response to oxygen (Dejours test)	at 36 weeks corrected postmenstrual age
Primary	Central chemoreceptor control of breathing function	Ventilatory response to carbon dioxide	at 32 weeks corrected postmenstrual age
Primary	Central chemoreceptor control of breathing function	Ventilatory response to carbon dioxide	at 36 weeks corrected postmenstrual age
Primary	Change in peripheral chemoreceptor control of breathing function	Ventilatory response to oxygen (Dejours test)	Change from 32 to 36 weeks postmenstrual age
Primary	Change in central chemoreceptor control of breathing function	Ventilatory response to carbon dioxide	Change from 32 to 36 weeks postmenstrual age
Secondary	Ventilatory stability - Apnea frequency	Frequency of apnea episodes per hour	at 32 and 36 weeks corrected postmenstrual age
Secondary	Ventilatory stability - Periodic breathing density	Percent of time with periodic breathing	at 32 and 36 weeks corrected postmenstrual age
Secondary	Ventilatory stability - Time series analysis of inter-breath interval	Tail slope of the log-scaled probability density function of the inter-breath time series	at 32 and 36 weeks corrected postmenstrual age
Secondary	Mechanisms of episodic hypoxemia	Classify etiology of episodes of hypoxemia as central, obstructive, or mixed apnea or active exhalation based on measurements of respiratory inductance plethysmography, esophageal pressure	at 32 and 36 weeks corrected postmenstrual age
Secondary	Apneic CO2 threshold in central apnea	Carbon dioxide level change at onset of central apnea	at 32 and 36 weeks corrected postmenstrual age
Secondary	Apneic CO2 threshold during mechanical ventilation	Carbon dioxide level change at onset of central apnea with stepwise increase in ventilator rate	at 32 and 36 weeks corrected postmenstrual age