Early NIRS: Cerebral Oxygenation and Autoregulation in Preterm Infants

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02147769
• Collaborator: Medtronic - MITG (Industry)
• Enrollment: 111
• Locations: 7
• Duration (Months): 46
• Patients Per Site: 15.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Premature infants are at high risk for variations in blood pressure and oxygenation during the first few days of life. The immaturity of the premature brain may further predispose these infants to death or the development of neurologic problems. The relationship between unstable blood pressure and oxygen levels and brain injury has not been well elucidated.

This study investigates the utility of near-infrared spectroscopy (NIRS), a non-invasive oxygen-measuring device, to identify preterm infants at highest risk for brain injury or death.

Condition or Disease	Intervention/Treatment	Phase
Intraventricular Hemorrhage of Prematurity; Complications of Prematurity	Device: NIRS monitoring

Study Design

• Study Type: Observational
• Actual Enrollment: 111 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Cerebral Oxygenation and Autoregulation in Preterm Infants: Association With Morbidity and Mortality
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Preterm infants monitored with NIRS All infants enrolled in the study will be monitored with cerebral near-infrared spectroscopy (NIRS monitoring) to measure cerebral oxygenation levels in the first 96 hours of life. Mean arterial blood pressure will simultaneously be monitored.	Device: NIRS monitoring; All enrolled infants will undergo NIRS monitoring of cerebral oxygenation in addition to monitoring of continuous arterial blood pressure.

Outcome Measures

Primary Outcome Measures

1. Mortality Before Hospital Discharge [Outcome measure will be assessed at the time of subject's initial discharge from the hospital (on average by 40 weeks postmenstrual age), but at a maximum of 1 year of life.]

   Participants will be followed for the outcome of death prior to hospital discharge.

2. Severe Central Nervous System (CNS) Morbidity [Outcome measure will be assessed on day 10 of life. Participants will be followed for neuroradiographic evidence of CNS morbidity in the first ten days of life]

   Routine cranial ultrasound obtained within the first ten days of life will be utilized to detect grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, significant ventriculomegaly, or white matter abnormalities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 24 Hours
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• inborn

• birth weight <= 1250 grams

• indwelling arterial catheter in place

• age <24 hours old

Exclusion Criteria:

• lethal chromosomal abnormality

• major congenital anomaly

• skin integrity insufficient to allow placement of NIRS sensors

• decision to not provide full intensive care

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35249
2	Stanford University	Palo Alto	California	United States	94304
3	Santa Clara Valley Medical Center	San Jose	California	United States	95128
4	Yale-New Haven Children's Hospital	New Haven	Connecticut	United States	06520
5	St. John's Children's Hospital	Springfield	Illinois	United States	62702
6	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
7	UT Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• Stanford University
• Medtronic - MITG

Investigators

• Principal Investigator: Valerie Chock, MD, Stanford University
• Principal Investigator: Krisa Van Meurs, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 18, 2016

More Information

Publications

• Alderliesten T, Lemmers PM, Smarius JJ, van de Vosse RE, Baerts W, van Bel F. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr. 2013 Apr;162(4):698-704.e2. doi: 10.1016/j.jpeds.2012.09.038. Epub 2012 Nov 6.
• Caicedo A, De Smet D, Naulaers G, Ameye L, Vanderhaegen J, Lemmers P, Van Bel F, Van Huffel S. Cerebral tissue oxygenation and regional oxygen saturation can be used to study cerebral autoregulation in prematurely born infants. Pediatr Res. 2011 Jun;69(6):548-53. doi: 10.1203/PDR.0b013e3182176d85.
• Soul JS, Hammer PE, Tsuji M, Saul JP, Bassan H, Limperopoulos C, Disalvo DN, Moore M, Akins P, Ringer S, Volpe JJ, Trachtenberg F, du Plessis AJ. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res. 2007 Apr;61(4):467-73.
• Verhagen EA, Hummel LA, Bos AF, Kooi EM. Near-infrared spectroscopy to detect absence of cerebrovascular autoregulation in preterm infants. Clin Neurophysiol. 2014 Jan;125(1):47-52. doi: 10.1016/j.clinph.2013.07.001. Epub 2013 Aug 22.
• Wong FY, Leung TS, Austin T, Wilkinson M, Meek JH, Wyatt JS, Walker AM. Impaired autoregulation in preterm infants identified by using spatially resolved spectroscopy. Pediatrics. 2008 Mar;121(3):e604-11. doi: 10.1542/peds.2007-1487. Epub 2008 Feb 4.
• Wong FY, Silas R, Hew S, Samarasinghe T, Walker AM. Cerebral oxygenation is highly sensitive to blood pressure variability in sick preterm infants. PLoS One. 2012;7(8):e43165. doi: 10.1371/journal.pone.0043165. Epub 2012 Aug 14.

• Responsible Party: Valerie Chock, M.D., M.S. Epi, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT02147769
• Other Study ID Numbers: 23894
• First Posted: May 28, 2014
• Last Update Posted: Apr 7, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Valerie Chock, M.D., M.S. Epi, Principle Investigator, Stanford University: cerebral autoregulation; preterm; near-infrared spectroscopy
• Additional relevant MeSH terms: Premature Birth; Hemorrhage

Study Results

Participant Flow

Arm/Group Title	Preterm Infants Monitored With NIRS
Arm/Group Description	All infants enrolled in the study will be monitored with cerebral near-infrared spectroscopy (NIRS monitoring) to measure cerebral oxygenation levels in the first 96 hours of life. Mean arterial blood pressure will simultaneously be monitored. NIRS monitoring: All enrolled infants will undergo NIRS monitoring of cerebral oxygenation in addition to monitoring of continuous arterial blood pressure.
Period Title: Overall Study
STARTED	111
COMPLETED	111
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Preterm Infants Monitored With NIRS
Arm/Group Description	All infants enrolled in the study will be monitored with cerebral near-infrared spectroscopy (NIRS monitoring) to measure cerebral oxygenation levels in the first 96 hours of life. Mean arterial blood pressure will simultaneously be monitored. NIRS monitoring: All enrolled infants will undergo NIRS monitoring of cerebral oxygenation in addition to monitoring of continuous arterial blood pressure.
Overall Participants	111
Age (Count of Participants)
<=18 years	111 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (weeks gestational age) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks gestational age]	26 (1.7)
Sex: Female, Male (Count of Participants)
Female	55 49.5%
Male	56 50.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	29 26.1%
Native Hawaiian or Other Pacific Islander	3 2.7%
Black or African American	18 16.2%
White	56 50.5%
More than one race	5 4.5%
Unknown or Not Reported	0 0%
Death or Neuroradiographic abnormality at baseline (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Mortality Before Hospital Discharge
Description	Participants will be followed for the outcome of death prior to hospital discharge.
Time Frame	Outcome measure will be assessed at the time of subject's initial discharge from the hospital (on average by 40 weeks postmenstrual age), but at a maximum of 1 year of life.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preterm Infants Monitored With NIRS
Arm/Group Description	All infants enrolled in the study will be monitored with cerebral near-infrared spectroscopy (NIRS monitoring) to measure cerebral oxygenation levels in the first 96 hours of life. Mean arterial blood pressure will simultaneously be monitored. NIRS monitoring: All enrolled infants will undergo NIRS monitoring of cerebral oxygenation in addition to monitoring of continuous arterial blood pressure.
Measure Participants	111
Count of Participants [Participants]	11 9.9%

2. Primary Outcome

Title	Severe Central Nervous System (CNS) Morbidity
Description	Routine cranial ultrasound obtained within the first ten days of life will be utilized to detect grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, significant ventriculomegaly, or white matter abnormalities.
Time Frame	Outcome measure will be assessed on day 10 of life. Participants will be followed for neuroradiographic evidence of CNS morbidity in the first ten days of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preterm Infants Monitored With NIRS
Arm/Group Description	All infants enrolled in the study will be monitored with cerebral near-infrared spectroscopy (NIRS monitoring) to measure cerebral oxygenation levels in the first 96 hours of life. Mean arterial blood pressure will simultaneously be monitored. NIRS monitoring: All enrolled infants will undergo NIRS monitoring of cerebral oxygenation in addition to monitoring of continuous arterial blood pressure.
Measure Participants	111
Count of Participants [Participants]	14 12.6%

Adverse Events

Time Frame	Adverse events were collected until hospital discharge or 6 months (whichever occurred first).
Arm/Group Title	Preterm Infants Monitored With NIRS
Arm/Group Description	All infants enrolled in the study will be monitored with cerebral near-infrared spectroscopy (NIRS monitoring) to measure cerebral oxygenation levels in the first 96 hours of life. Mean arterial blood pressure will simultaneously be monitored. NIRS monitoring: All enrolled infants will undergo NIRS monitoring of cerebral oxygenation in addition to monitoring of continuous arterial blood pressure.
All Cause Mortality
	Preterm Infants Monitored With NIRS
	Affected / at Risk (%)	# Events
Total	11/111 (9.9%)
Serious Adverse Events
	Preterm Infants Monitored With NIRS
	Affected / at Risk (%)	# Events
Total	14/111 (12.6%)
Nervous system disorders
CNS abnormality	14/111 (12.6%)	14
Other (Not Including Serious) Adverse Events
	Preterm Infants Monitored With NIRS
	Affected / at Risk (%)	# Events
Total	0/111 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.