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

April 30, 2021 updated by: Fleur Anne Camfferman, Universitair Ziekenhuis Brussel

Sonographic Quantification of Venous Circulation in the Preterm Brain

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)

Study Overview

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).

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 3 hours (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Preterm infants < 28 weeks gestational age
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).
Other: Preterm infants born between 28 0/7 and 31 6/7 weeks
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.
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Normative values of internal cerebral vein velocity
Time Frame: 2-3 years

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.

2-3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Short-term outcome: cerebral complications in the neonatal phase
Time Frame: 2-3 years
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.
2-3 years
Long-term outcome: neurodevelopmental impairment
Time Frame: 3-5 years
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.
3-5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Paul Govaert, MD PhD, Universitair Ziekenhuis Brussel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

August 27, 2020

First Submitted That Met QC Criteria

August 27, 2020

First Posted (Actual)

September 2, 2020

Study Record Updates

Last Update Posted (Actual)

May 3, 2021

Last Update Submitted That Met QC Criteria

April 30, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Intraventricular Hemorrhage

Clinical Trials on Doppler Ultrasound of venous cerebral circulation

3
Subscribe