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Sonographic QUantification of Venous Circulation In the Preterm Brain (SQUIB)

Primary Purpose

Prematurity; Extreme, Cerebral Circulatory Failure, Intraventricular Hemorrhage

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Doppler Ultrasound of venous cerebral circulation
Sponsored by
Universitair Ziekenhuis Brussel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Prematurity; Extreme focused on measuring Preterm infant, extremely preterm infant, Cerebral circulation, Venous Flow, Internal Cerebral Vein, Neurodevelopmental outcome, Intraventricular Hemorrhage, Periventricular Leukomalacia

Eligibility Criteria

undefined - 3 Hours (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Preterm infant with a gestational age below 32 0/7 weeks
  • birth weight between the 3rd and 97th percentile.
  • No cerebral Doppler abnormalities on prenatal ultrasound (i.e. brain sparing)

Exclusion Criteria:

  • Brain vessel anomaly
  • Major congenital malformation
  • No parental consent
  • IVH > grade 2 (Papile classification or structural brain abnormalities on the first ultrasound
  • Severe hemodynamic instability in the first 6 hours of life requiring treatment with inotropes.

Sites / Locations

  • UZ BrusselRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Preterm infants < 28 weeks gestational age

Preterm infants born between 28 0/7 and 31 6/7 weeks

Arm Description

For infants born before 28 0/7 weeks, standard of care consists of brain ultrasound performed on admission, day 1, day 2, day 3, day 7, and then weekly until discharge.

For infants born between 28 0/7 and 31 6/7 weeks, brain ultrasound is performed on admission, once between day 1 and 3, once between day 7 and 10, and then 2-weekly until discharge or transfer.

Outcomes

Primary Outcome Measures

Normative values of internal cerebral vein velocity
Determination of normative values of ICV velocity and their range in the first weeks of life in stable preterm infants. The Doppler measurements will be performed at several moments after birth: day 0, 1, 2, 3, 7, 14, 21, etc untill 36 weeks gestational age. For this purpose we will calculate the Maximum velocity (cm/s), the mean velocity (cm/s) and the variability (according to Ikeda et al) of the flow pattern in the Internal Cerebral Vein. These velocities will be plotted in an attempt to discover longitudinal normative values in this cohort of 50 preterm infants.

Secondary Outcome Measures

Short-term outcome: cerebral complications in the neonatal phase
Relation of ICV flow with IVH grade 2 or more (according to the Papile classification), periventricular leukomalacia, ventriculomegaly, white matter disease, selective neuronal necrosis assessed by routinely performed MRI scan of the brain at term equivalent age.
Long-term outcome: neurodevelopmental impairment
Relation of ICV flow with Bayley mental and motor scales at 2 years of age, as rou-tinely performed by the COS - Centrum voor Ontwikkelingsstoornissen.

Full Information

First Posted
August 27, 2020
Last Updated
April 30, 2021
Sponsor
Universitair Ziekenhuis Brussel
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1. Study Identification

Unique Protocol Identification Number
NCT04535375
Brief Title
Sonographic QUantification of Venous Circulation In the Preterm Brain
Acronym
SQUIB
Official Title
Sonographic Quantification of Venous Circulation in the Preterm Brain
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universitair Ziekenhuis Brussel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of the study is to develop an accessible, reproducible ultrasound tool for objective clinical measurement of brain circulation in preterm infants in order to identify infants being at risk for preterm brain injury at an early stage. In the future, the results of this study might be useful to select those infants for early interventions aimed at preventing brain injury. In this study we will identify the normative values of the internal cerebral vein velocity in a reference cohort of stable preterm infants. This stable group of preterm infants is defined as all preterm infants with a birth weight appropriate for gestational age, and without major complications (such as a severe intracranial hemorrhage, severe hemodynamical instability, birth asphyxia) or major congenital malformations. In this group we will identify subgroups based on moments of clinical instability (sepsis, temporary hypotension, NEC, need for invasive respiratory support) or based on outcome parameters (IVH, PVL, developmental outcomes)
Detailed Description
The aim of the study is to develop an accessible, reproducible ultrasound tool for objective clinical measurement of brain circulation in preterm infants in order to identify infants being at risk for preterm brain injury at an early stage. In the future, the results of this study might be useful to select those infants for early interventions aimed at preventing brain injury. In this study we will identify the normative values of the internal cerebral vein velocity in a reference cohort of stable preterm infants. This stable group of preterm infants is defined as all preterm infants with a birth weight appropriate for gestational age, and without major complications (such as a severe intracranial hemorrhage, severe hemodynamical instability, birth asphyxia) or major congenital malformations. In this group we will identify subgroups based on moments of clinical instability (sepsis, temporary hypotension, NEC, need for invasive respiratory support) or based on outcome parameters (IVH, PVL, developmental outcomes) Serial brain ultrasound examinations are routinely performed as standard of care after preterm birth for timely de-tection of brain hemorrhage in the first week of life and brain injury in the weeks thereafter until term equivalent age. For infants born between 28 0/7 and 31 6/7 weeks, brain ultrasound is performed on admission, once between day 1 and 3, once between day 7 and 10, and then 2-weekly until discharge or transfer. For infants born before 28 0/7 weeks, standard of care consists of brain ultrasound performed on admission, day 1, day 2, day 3, day 7, and then weekly until discharge. No additional ultrasound examinations, specifically for the purpose of this study, will be performed. Instead, with each routine ultrasound examination, additional images on top of the routine frames will be collected. Those images will document the velocity and flow in the internal cerebral veins bilaterally using the standard Color Doppler tech-nique. Taking these additional images will prolong the time of ultrasound examination only minimally (with a few minutes). The ultrasound will be performed using a standardized ultrasound protocol according to Ecury-Goossen et al (18) us-ing the Esaote MyLab Twice (Genova, Italy) with a linear (Esaote LA 435 Linear Array Ultrasound Probe, 6.0-18.0 MHz) and convex probe (Esaote CA123 Convex Array Ultrasound Probe, 3.3-9.0 MHz). This is the standard ultra-sound machine for ultrasound investigations at our neonatology ward. For routine cranial ultrasound, ten images are generally made through the anterior fontanelle: five in the coronal and five in the sagittal plane. In addition to that, color Doppler or power Doppler is commonly performed in one of the pericallosal arteries in order to evaluate the arterial circulation, quantified by calculating a resistency index (RI). Usually routine ultrasound takes up to 10-15 minutes. After routine scanning, four extra images will be acquired. These are power doppler images, one per insonated ves-sel of interest. The vessels of interest are the internal cerebral vein (left and right separate, if feasible) and one small tributary (the posterior caudate vein) on each side. To derive these images the duration of the US will be prolonged with approximately 3-5 minutes. Blood flow velocities (maximum velocity and velocity pattern (17)) can be calculated offline in the anonymously ex-ported dicom file of these four images. In addition to the ultrasound data, the following clinical patient data will be collected during the study: Data on systemic perfusion immediately before each ultrasound: arterial blood pressure, mixed cerebral oxygen saturation using near infrared spectroscopy (NIRS), fractional oxygen extraction, limb oxygen satu-ration, heart rate and use of inotropes. Demographic data during hospitalization, such as gender, gestational age, birth weight, head circumfer-ence and complications during hospitalization (infection, surgery, etcetera).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prematurity; Extreme, Cerebral Circulatory Failure, Intraventricular Hemorrhage, Periventricular Leukomalacia
Keywords
Preterm infant, extremely preterm infant, Cerebral circulation, Venous Flow, Internal Cerebral Vein, Neurodevelopmental outcome, Intraventricular Hemorrhage, Periventricular Leukomalacia

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
All stable preterm infants born before a gestational age of 32 weeks are eligible for inclusion. Since standard ultrasound protocol is different for preterm infants born below or after 28 weeks, two subgroups will be created.
Masking
Outcomes Assessor
Masking Description
Extra ultrasound images will be exported anonymized and analyses offline by two investigators independently
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Preterm infants < 28 weeks gestational age
Arm Type
Other
Arm Description
For infants born before 28 0/7 weeks, standard of care consists of brain ultrasound performed on admission, day 1, day 2, day 3, day 7, and then weekly until discharge.
Arm Title
Preterm infants born between 28 0/7 and 31 6/7 weeks
Arm Type
Other
Arm Description
For infants born between 28 0/7 and 31 6/7 weeks, brain ultrasound is performed on admission, once between day 1 and 3, once between day 7 and 10, and then 2-weekly until discharge or transfer.
Intervention Type
Diagnostic Test
Intervention Name(s)
Doppler Ultrasound of venous cerebral circulation
Intervention Description
No additional ultrasound examinations, specifically for the purpose of this study, will be performed. Instead, with each routine ultrasound examination, additional images on top of the routine frames will be collected. Those images will document the velocity and flow in the internal cerebral veins bilaterally using the standard Color Doppler tech-nique. Taking these additional images will prolong the time of ultrasound examination only minimally (with a few minutes).
Primary Outcome Measure Information:
Title
Normative values of internal cerebral vein velocity
Description
Determination of normative values of ICV velocity and their range in the first weeks of life in stable preterm infants. The Doppler measurements will be performed at several moments after birth: day 0, 1, 2, 3, 7, 14, 21, etc untill 36 weeks gestational age. For this purpose we will calculate the Maximum velocity (cm/s), the mean velocity (cm/s) and the variability (according to Ikeda et al) of the flow pattern in the Internal Cerebral Vein. These velocities will be plotted in an attempt to discover longitudinal normative values in this cohort of 50 preterm infants.
Time Frame
2-3 years
Secondary Outcome Measure Information:
Title
Short-term outcome: cerebral complications in the neonatal phase
Description
Relation of ICV flow with IVH grade 2 or more (according to the Papile classification), periventricular leukomalacia, ventriculomegaly, white matter disease, selective neuronal necrosis assessed by routinely performed MRI scan of the brain at term equivalent age.
Time Frame
2-3 years
Title
Long-term outcome: neurodevelopmental impairment
Description
Relation of ICV flow with Bayley mental and motor scales at 2 years of age, as rou-tinely performed by the COS - Centrum voor Ontwikkelingsstoornissen.
Time Frame
3-5 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
3 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Preterm infant with a gestational age below 32 0/7 weeks birth weight between the 3rd and 97th percentile. No cerebral Doppler abnormalities on prenatal ultrasound (i.e. brain sparing) Exclusion Criteria: Brain vessel anomaly Major congenital malformation No parental consent IVH > grade 2 (Papile classification or structural brain abnormalities on the first ultrasound Severe hemodynamic instability in the first 6 hours of life requiring treatment with inotropes.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fleur A Camfferman, MD
Phone
02 477 7721
Email
Fleur.Camfferman@uzbrussel.be
First Name & Middle Initial & Last Name or Official Title & Degree
Filip Cools, MD PhD
Phone
02 477 7721
Email
Filip.Cools@uzbrussel.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Govaert, MD PhD
Organizational Affiliation
Universitair Ziekenhuis Brussel
Official's Role
Study Chair
Facility Information:
Facility Name
UZ Brussel
City
Brussel
State/Province
Brussels Capital
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fleur A Camfferman, MD
Phone
024777721
Email
Fleur.Camfferman@uzbrussel.be
First Name & Middle Initial & Last Name & Degree
Filip Cools, MD PhD
Phone
024777721
Email
Filip.Cools@uzbrussel.be

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
For future systematic reviews anonimized individual participant data can be made available is an e-mail request is addressed at the principal investigator.
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Sonographic QUantification of Venous Circulation In the Preterm Brain

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