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Prematurity-Related Ventilatory Control (PreVent)

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ClinicalTrials.gov Identifier: NCT03464396
Recruitment Status : Recruiting
First Posted : March 14, 2018
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The purpose of this research study is to improve our understanding of unstable breathing and heart blood flow patterns seen in premature infants. The investigator will use novel non-invasive measures to understand the determinants of these unstable breathing and heart flow patterns to potentially identify new therapies for their prevention.

Condition or disease Intervention/treatment
Respiratory Control in Premature Infants Other: Bedside Physiology study Other: Carotid Body Function Test Other: Room Air Challenge Other: Hypoxia Challenge Test Other: Effects of Nasal Cannula Flow Diagnostic Test: Magnetic Resonance Imaging Diagnostic Test: Echocardiogram Other: Blood Sample

Detailed Description:

The investigator will look at results of breathing tests, non-invasive sound wave (ultrasound) test of the heart and blood vessel (Echocardiography), and a sample of blood to see if it is possible for early detection of breathing control and lung blood vessel dysfunction (pulmonary vascular disease) in infants that are at risk for exposure to long term low oxygen levels. A subset of infants will have a magnetic resonance Imaging study (MRI) between 37- 40 weeks gestational age (GA) or at the time of discharge, whichever comes first.

Respiratory tests include:

  • Bedside Physiology Study completed at 28, 32, 36, 40, and 52 weeks gestational age (GA) in conjunction with the respiratory tests. A 90-minute recording will be made using standard recording equipment that includes a conventional pulse oximeter, an EEG, an airflow sampling catheter near the nose, and respiratory inductance plethysmography (RIP) bands. Standard bedside monitoring will continue during the physiologic studies
  • Carotid Body Function Test completed at 32, 36, 40 and 52 weeks GA. This test is to unmask respiratory instability in response to hyperoxia.
  • Challenge Test completed at 36 weeks GA.

    1. Infants receiving nasal cannula flow with or without supplemental oxygen will undergo a Room Air Challenge Test.
    2. Infants on RA alone will undergo a Hypoxia Challenge test.
  • Effects of Nasal Cannula Flow completed at 28, 32, 36, 40 and 52 week's GA. The flow will be increased through a nasal cannula. This test is to see how flow effects the breathing pattern.

A subset of infants will have an MRI between 37-40 weeks GA or before discharge, whichever comes first. The MRI will allow the doctors to look and see if there is any injury present in the brain that can be linked to an abnormal breathing pattern called periodic breathing.

A subset of infants will have an Echocardiogram (Echo) at 32, 36 and 52 weeks GA. The Echo is performed to assess cardiac structure and function. Echocardiography is performed routinely in premature newborns in the Neonatal Intensive Care Unit (NICU). The echocardiogram will be performed at the infant bedside and will be coordinated with bedside nurse. The infant will remain on a cardio-respiratory monitor during the echocardiogram for approximately 15 minutes.

Infants that have an Echo will have a blood sample collected near the time of the Echo, 3-blood samples total. The purpose of collecting the blood sample is to detect if the Fibroblast Growth Factor (FGF2) level is elevated and possibly be a biomarker of early pulmonary hypertension in pre term infants validated with the echo.


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Study Type : Observational
Estimated Enrollment : 375 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Physiologic Biomarkers Predicting Ventilatory Instability and Hypoxemia in Pre Mature Infants
Actual Study Start Date : May 14, 2018
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 30, 2021

Group/Cohort Intervention/treatment
Preterm infant study visits

Preterm infants Study Visits

  1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA.
  2. Respiratory tests:

    • Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA
    • Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA
    • Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA
  3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first.
  4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA
  5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Other: Bedside Physiology study
A 90-minute recording in conjunction with the respiratory evaluations using standard recording equipment that includes a conventional pulse oximeter, an EEG, an airflow sampling catheter near the nose, and respiratory inductance plethysmography (RIP) bands. Standard clinical bedside monitoring will continue during the respiratory evaluations.

Other: Carotid Body Function Test
Infants without nasal cannula will have a nasal cannula placed in their nares. After a 15-minute baseline period and during quiet sleep, the infant will then be exposed to 30 seconds of 100% O2 by increasing FiO2. This test will be repeated 3 times, with at least 3 minutes between tests to allow for return of SpO2 to baseline values. If oxygen saturations increase to 99% for 15 seconds or the infant is apneic for greater than 5 seconds following initiation of 100% O2, the test will be stopped and FiO2 brought back to baseline. Infants in the NICU will be monitored continuously with heart rate, respiratory rate, and SpO2% for 12 hours after Carotid Body Function Test according to NICU standards. Infants discharge who return for Carotid Body Function Test at 40 and 52 weeks PMA will be monitored continuously for 1 hour after the test is finished.

Other: Room Air Challenge
Infants receiving nasal cannula high flow support 3 liters per minute (LPM) or less with or without supplemental O2 at 36 weeks PMA will be eligible. After a 15-minute quiet sleep period, infants' FiO2 will be weaned, in 0.20 decrements for 5 min intervals. Flow then decreased in 10 min intervals, initially in 1 LPM decrement until nasal cannula flow is 1LPM, and then decreased by 50% decrements to 0.125 LPM then off. If the infant is weaned to room air alone for 15 minutes, not meeting failure criteria, he/she has passed the RAC. Failure of the RAC is defined as occurring when SpO2% falls below 80%, even briefly, or remains less than 90% for 5 consecutive minutes any time during the test, bradycardia (HR < 80 bpmx 10 sec) or persistent apnea despite stimulation. Infant is returned to the level of support provided before the RAC begun if meets any failure criteria.
Other Name: RAC

Other: Hypoxia Challenge Test
Infant's breathing room air alone at 36 weeks PMA are eligible. A nasal cannula will be placed prior to a 15-minute period of quiet sleep. During the 15 minutes of quiet sleep, the infant is required to maintain a SpO2 of > 92% in order to undergo the HCT. After the15-minute baseline recording, HCT will begin using FiO2 = 0.18 for 5 minutes. If infant does not meet failure criteria, infant will be given FiO2 0.15 for 10 minutes. Failure criteria is SpO2% < 80% even briefly, or SpO2% 80% to 85% for 30 seconds, bradycardia (HR < 80 bpmx 10 sec) or persistent apnea despite stimulation. If an infant meets criterion for failure, supplemental O2 with FiO2 100% will be started until SpO2% is sustained between 90% and 95%. At that time, the infant will be returned to RA.
Other Name: HCT

Other: Effects of Nasal Cannula Flow

Infants will have a standard nasal catheter in place at time of testing (NeoTech Premature RAM Cannula). A 15-minute baseline recording of all physiologic study parameters prior to initiation. Tested in three groups of infants.

  1. 28 and 32 weeks PMA flow rates increased after a 15-minute baseline period to 3LPM, or by 1LPM to a max of 5LPM for duration of 15 minutes.
  2. Infant's that fail the RAC or HCT at 36 weeks with periodic breathing will have high flow at 3LPM started for 2 minutes or until periodic breathing stops.
  3. Breathing room air alone at 40 and 52 weeks PMA will have a high flow catheter inserted in their nares. If they have periodic breathing lasting longer than 1 minute during the 15-minute baseline period, flow at 3LPM will be started and maintained for 2 minutes or until periodic breathing stops.

Diagnostic Test: Magnetic Resonance Imaging
A non-sedating MRI scan will be performed on 3 subsets of infants at 37-40 weeks PMA, or when infant is within one week of discharge from the NICU. Standard images as well as research images will be obtained. The research images use the same MRI scanner and collection techniques as standard clinical imaging, but provide a more detailed examination of brain anatomy and injury. Collection of these sequences using our standard non-sedated acquisition practices for infants is well tolerated. Infants will be placed in scanner by registered nurse accompanied by radiology technician to assure infants' comfort during scan. Infant will remain on cardio-respiratory monitor during MRI via a pulse oximetry probe. It will take no longer than one hour to complete MRI scan including transportation to radiology unit.
Other Name: MRI

Diagnostic Test: Echocardiogram
An echocardiogram (referred to as an ultrasound of the heart on the consent form) will be performed to assess cardiac structure and function. Echocardiograms are performed routinely in premature newborns in the NICU. The Echocardiogram will be performed at the infant bedside and will be coordinated with bedside nurse. The infant will remain on a cardio-respiratory monitor during the echocardiogram for approximately 15 minutes.
Other Name: Echo

Other: Blood Sample
Infants that have echocardiograms will have a blood sample collected near the time the echocardiogram is obtained, 3-blood samples total. The blood sample will only be collected with parental permission on an opt-in or out-basis and collected only with routine clinical labs.




Primary Outcome Measures :
  1. Respiratory phenotype based on physiologic testing [ Time Frame: 36 weeks post menstrual age ]
    Categorization of subjects based on physiologic Challenge Tests into one of four respiratory phenotypes.


Biospecimen Retention:   Samples With DNA
Buccal Swabs


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Ages Eligible for Study:   up to 7 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Infants admitted to the Neonatal Intensive Care Unit who are born between 24 0/7 to 28 7/8 weeks GA
Criteria

Inclusion Criteria:

  • All infants born between 24 0/7 and 28 6/7 weeks GA admitted to the Neonatal Intensive Care Unit at St. Louis Children's Hospital will be considered for enrollment.

Exclusion Criteria:

  • Infants not likely to survive
  • Infant with significant heart disease
  • Infant with a significant congenital abnormalities of the central nervous system, nose, mouth lungs or ribs, or congenital diseases that affect lung growth
  • Physician refusal
  • Unlikely that the infant will be available for 52-week follow-up visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03464396


Contacts
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Contact: Julie A Hoffmann, RN 314-273-1990 hoffmann_j@wustl.edu
Contact: Barbara Warner, MD 314-424-7115 warner_b@kids.wustl.edu

Locations
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United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Julie A Hoffmann, RN    314-273-1990    hoffmann_j@wustl.edu   
Contact: Laura Linneman, RN    314-454-1990    linneman_l@wustl.edu   
Principal Investigator: James Kemp, MD         
Sponsors and Collaborators
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: James Kemp, MD Washington University School of Medicine

Publications:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03464396     History of Changes
Other Study ID Numbers: 201611138
5U01HL133700-02 ( U.S. NIH Grant/Contract )
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Washington University School of Medicine:
Periodic breathing
Apnea of prematurity
Chronic Lung disease
Prematurity
Respiratory disease
Hypoxia
Pulmonary Hypertension
Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications