Brain InjuriesPBSFNCT03786497
Protecting Brains and Saving Futures - the PBSF Protocol
An observational study of Brain Injuries and Congenital Heart Disease, run by Protecting Brains Saving Futures at 2 sites in Brazil.
Trial summary
Background: Multiple neonatal disorders are associated with risks of neurological injury. Thus, management of these infants should involve a coordinated approach to permit early diagnosis with improved clinical care. Read more about this study
- Who is it for?
- Ages Up to 3 months
- Conditions the study is for
- Brain Injuries, Congenital Heart Disease, Newborn Morbidity
- How many people
- 2,268 participants
- Where
- 2 sitesBrazil
- Study dates
- 1 Jan 2021to 31 Dec 2023
- How long will I take part?
- 24 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 3 months
- All sexes
- No healthy volunteers
- Child
Study population: This will be a multicenter, prospective, observational study in a cohort of high-risk neonates treated at 20 different Neonatal Intensive Care Units in terciary hospitals in Brazil.
Who may be able to join
None listed.
Who cannot join
- Patients with genetic syndromes or malformation incompatible with life, or older than three months old will be excluded.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Irmandade da Santa Casa de Misericórdia de São Paulo
São Paulo, São Paulo, 01221-010
Maurício Maralhães, MD, 5511999330294, m-magalhaes@uol.com.br
Rafaela FR Pietrobom, MD, 5511949724721, rafaela.fabri@pbsf.com.br
Protecting Brains and Saving Futures - PBSF
São Paulo, 01407-000
Gabriel FT Variane, MD, 5511996243520, gabriel.variane@pbsf.com.br
Alexandre Netto, MD, +5511993284856, alexandre.netto@pbsf.com.br
About this study
Official title: Protecting Brains and Saving Futures - the PBSF Protocol: a Prospective Multicenter and Observational Study on the Use of Telemedicine for Neurocritical Care in High-risk Newborns in Brazil.
Background: Multiple neonatal disorders are associated with risks of neurological injury. Thus, management of these infants should involve a coordinated approach to permit early diagnosis with improved clinical care. Such initiative involves the use of standardized protocols, continuous and specialized brain monitoring with electroencephalography (EEG), amplitude integrated EEG (aEEG) and Near Infrared Spectroscopy (NIRS), neuroimaging and training. Brazil is a very large country with disparities in health care assessment; some neonatal intensive care units (NICUs) are not well structured and trained to provide adequate neurocritical care. However, the development and implementation of these neurocritical care units requires high expertise and significant investment of time, manpower and equipment. In order to reduce the existing gap, a unique advanced telemedicine model of neurocritical care called Protecting Brains and Saving Futures (PBSF) protocol was developed and implemented in some Brazilian NICUs.
Methods: A prospective observational cohort study will be conducted in 20 Brazilian NICUs that have adopted the PBSF protocol. All infants receiving the protocol during January 2021 to December 2023 will be eligible. Ethical approval will be obtained from the participating institutions. The primary objective is to describe the use of the PBSF protocol and clinical outcomes, by center and over a 3 years period. The use of the PBSF protocol will be measured by quantification of neuromonitoring, neuroimaging exams and sub-specialties consultation. Clinical outcomes of interest after the protocol implementation are length of hospital stay, detection of EEG seizures during hospitalization, use of anticonvulsants, inotropes, and fluid resuscitation, death before hospital discharge, and referral of patients to high-risk infant follow-up. These data will be also compared between infants with primarily neurologic and primarily clinical diagnosis.
Discussion: The implementation of the PBSF protocol may provide adequate remote neurocritical care in high-risk infants with optimization of clinical management and improved outcomes. Data from this large, prospective, multicenter study are essential to determine whether neonatal neurocritical units can improve outcomes. Finally, it may offer the necessary framework for larger scale implementation and help in the development of studies of remote neuromonitoring.
Read the detailed description
METHODS Objectives The aim of this multicenter, prospective, cohort study is to describe the use of the PBSF protocol and clinical outcomes, by center and over a 3 years period (2021 to 2023) in the NICUs that have adopted it. We hypothesize that the use of the PBSF protocol will increase over time with improvement of some specific short-term outcomes (see methods below). Results of this study may provide the necessary background information for larger studies and initiatives aiming to protect neonatal brains and save futures.
Study Design and Setting This will be a multicenter, prospective, observational study in a cohort of high-risk neonates treated at 20 different NICU's in Brazil. The intended period of patient recruitment and data collection will be 3 years (January 2021 to December 2023). The study followed the precepts of good clinical practice and was approved by the Research Ethics Committee of the Irmandade da Santa Casa de Misericórdia de São Paulo. In addition, the project has received formal authorization from the Clinical and Administrative Board of each center. When selecting a participant, the principal investigator of the study or one of the co-investigators will contact the parents or guardians and obtain informed consent. All data will be treated anonymously and confidentially, and in no phase of the study any name, image, or data that allows participants identification will be disclosed.
Participants In this cohort study, all the infants admitted to any of the 20 NICUs from birth up to three months of life and receiving the PBSF protocol are eligible. Indications for the use of the protocol are provided on Box 1. Patients with genetic syndromes or malformation incompatible with life, or older than three months old will be excluded. Details on the PBSF protocol are provided in supplemental material. Briefly, the protocol includes provision of equipment and resources, connection between the associated NICU and the remote monitoring center called the Central of Surveillance and Intelligence (CSI), training and teaching of all health care professional team of each NICU, and customized multiparametric recordings of biological signals of each patient monitoring. At the CSI, a team is available 24 hours a day all year around, allowing for case discussions and simplified reports of brain monitoring information on the patient monitor's display every 6 hours.
Variables Population demographics: gender, gestational age at birth, gestational age ≤ 32 weeks and < 37 weeks, Apgar score at 1 min, 5 min and 10 min, birth weight, current weight, inborn or outborn, use of antenatal steroids and magnesium sulfate, type of birth.
Primary diagnosis: seizure, anoxia/mild HIE, moderate or severe HIE/cooling, neurologic abnormalities without specific diagnosis, congenital central nervous system (CNS) anomalies, grade III or IV intraventricular hemorrhage (IVH) or hydrocephalus, periventricular leukomalacia, meningitis, neural tube defects, stroke, cyanotic congenital heart defect (CHD), prematurity, gestational age ≤ 32 weeks, meconium aspiration syndrome, cardiorespiratory instability, necrotizing enterocolitis, metabolic disease, extracorporeal membrane oxygenation (ECMO)/pre-ECMO and any other medical conditions not listed here.
For descriptive analysis of the 2 main outcomes (use of the PBSF protocol and clinical outcomes) patients will be them divided into two groups accordingly to their primary diagnosis: neurological or clinical.
Data sources / measurement Patient demographics, diagnosis and clinical outcomes will be extracted from the medical charts of each patient enrolled and entered in the PBSF database. The use of the PBSF protocol will be measured with the data collected by the CSI center continuously. Details of these recordings are provided on Appendix 2.
Bias To address potential source of bias related to financial availability, the 2 main outcomes of interest will be also adjusted based on the unit primary profile: private, foundation or public.
Study size Based on our current experience, there are an average of 5 patients per month with criteria for neurocritical care on each center, making a total of 3,240 eligible patients during a three years period. Considering a 30% loss due to refusal to consent, non-availability of the research team or missing data, we expect to recruit 2,268 infants from all study centers (around 756 patients per year).
Statistical methods Categorical variables will be analyzed by descriptive statistics and presented as number of valid cases and percentage (%). Numeric variables will be analyzed as mean and standard deviation, median and interquartile ranges, or coefficient intervals. Chi-square test (or Fisher's exact test) will be performed to analyze categorical variables and the Student's t test, or Wilcoxon rank sum test will be used to check for significant differences between the two groups. A p value of <0.05 will be considered statistically significant. The confidence interval considered will be 95%. Analysis of variability (distribution) per site for each variable of the 2 main outcomes will also be performed. ANOVA with post hoc Bonferroni will be used to compare outcomes over time, i.e. between years 1, 2 and 3 and Kaplan Meier curves will be generated to follow the evolution of outcomes over time for the 2 groups of patients: neurologic and clinical.
Results Participants. A flow chart of all eligible and enrolled patients will be produced, and the total number of patients will be reported, overall and per center.
Descriptive data Population demographics: male, n (%); gestational age at birth, weeks, mean (SD); gestational age ≤ 32 wk, n(%); Gestational age < 37 wk, n (%); Apgar score at 1 min, at 5 min, and at 10min, median (IQR); birth weight, grams, mean (SD); current weight, grams, mean (SD); Inborn, n (%); use of antenatal steroids and magnesium sulfate, n (%); Caesarean, n(%).
Primary outcomes:
Use of the PBSF protocol
- Use of aEEG/EEG monitoring
- Duration of aEEG/EEG monitoring
- Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)
- Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)
- Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.
- Number of clinical case discussions and videoconference meetings
Clinical outcomes
- Length of hospital stay
- Number of electroencephalographic seizures during hospitalization
- Use and types of anticonvulsants administered
- Number and types of anticonvulsants prescribed at discharge
- Use and types of inotropes administered during NICU stay
- Use and types of fluid resuscitation administered during NICU stay
- Death before hospital discharge
- Number of patients referred to neurology or neurosurgery
- Number of patients referred to high-risk infant follow-up*
Secondary outcomes:
Use of the PBSF protocol
- Number of remote communications between CSI and local team
- Number of reports issued for aEEG / EEG exams with or without the use of NIRS
- Number of patients who performed Therapeutic Hypothermia
- Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization
- Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay
- Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension
- Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning
- Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life
- Conditions
- Brain Injuries, Congenital Heart Disease, Newborn Morbidity, Intraventricular Hemorrhage, CNS Infection, Neonatal Seizure
- Keywords
- Newborn, Neonatal Neurocritical Care Units, Neonatal Brain Monitoring, Brain Injury, Neuroprotection, Telemedicine, Electroencephalography, Amplitude-Integrated Electroencephalography, Near Infrared Spectroscopy, Neurodevelopmental Problems
- Medical subject headings
- Brain Injuries, Heart Defects, Congenital, Central Nervous System Infections, Cross Infection, Hypoxia-Ischemia, Brain, Metabolism, Inborn Errors, Perinatal Death
What is being measured
The primary outcome is the main question the study is designed to answer.
Applicability of telemedicine model for monitored infants
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Applicability of telemedicine model for recorded remote monitoring
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Use of aEEG/EEG monitoring
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Duration of aEEG/EEG monitoring
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of clinical case discussions and videoconference meetings
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Length of hospital stay
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of electroencephalographic seizures during hospitalization
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Use and types of anticonvulsants administered
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number and types of anticonvulsants prescribed at discharge
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Use and types of inotropes administered during NICU stay
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Use and types of fluid resuscitation administered during NICU stay
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Death before hospital discharge
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of patients referred to neurology or neurosurgery
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of patients referred to high-risk infant follow-up
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Secondary outcomes (8)
Number of remote communications between CSI and local team
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of reports issued for aEEG / EEG exams with or without the use of NIRS
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Number of patients who performed Therapeutic Hypothermia
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Measured: 3 years period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start1 Jan 2021 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (83)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,268 participants (estimated)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- Protecting Brains Saving Futures
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Gabriel Variane, Protecting Brains Saving Futures
- Investigators
- Guilherme M Sant'Anna, PhD, Study director, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03786497
- Sponsor's protocol ID
- PBSF_2020
- Acronym
- PBSF
- Status last verified
- Nov 2020
- First submitted
- 12 Dec 2018
- Last updated
- 16 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329-38. doi: 10.1016/j.earlhumdev.2010.05.010. Epub 2010 Jun 16.
PubMed 20554402Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. doi: 10.1016/S0140-6736(05)71048-5.
PubMed 15752534Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000. Int J Epidemiol. 2006 Jun;35(3):706-18. doi: 10.1093/ije/dyl043. Epub 2006 Mar 23.
PubMed 16556647Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991 May;25(2):135-48. doi: 10.1016/0378-3782(91)90191-5.
PubMed 1713544Robertson CMT. Long-term follow-up of term infants with perinatal asphyxia. In: Stevenson DK, Benitz WE, Sunshine P. Fetal and neonatal brain injury. 3. Ed. New York: Cambridge University; 2003. p.829-58.
de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010 May;95(3):F220-4. doi: 10.1136/adc.2008.148205.
PubMed 20444814Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F380-7. doi: 10.1136/adc.2004.067520.
PubMed 16113154Blencowe H, Lee AC, Cousens S, Bahalim A, Narwal R, Zhong N, Chou D, Say L, Modi N, Katz J, Vos T, Marlow N, Lawn JE. Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatr Res. 2013 Dec;74 Suppl 1(Suppl 1):17-34. doi: 10.1038/pr.2013.204.
PubMed 24366461Hellstrom-Westas L, Rosen I. Continuous brain-function monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med. 2006 Dec;11(6):503-11. doi: 10.1016/j.siny.2006.07.011. Epub 2006 Oct 24.
PubMed 17067863Hellström-Westas L, Rosén I, de Vries LS, Greisen G. Amplitude-integrated EEG Classification and Interpretation in Preterm and Term Infants. NeoReviews. 2006;7(2):e76-87.
Shah DK, Mackay MT, Lavery S, Watson S, Harvey AS, Zempel J, Mathur A, Inder TE. Accuracy of bedside electroencephalographic monitoring in comparison with simultaneous continuous conventional electroencephalography for seizure detection in term infants. Pediatrics. 2008 Jun;121(6):1146-54. doi: 10.1542/peds.2007-1839.
PubMed 18519484Mastrangelo M, Fiocchi I, Fontana P, Gorgone G, Lista G, Belcastro V. Acute neonatal encephalopathy and seizures recurrence: a combined aEEG/EEG study. Seizure. 2013 Nov;22(9):703-7. doi: 10.1016/j.seizure.2013.05.006. Epub 2013 May 29.
PubMed 23725740Shah DK, Zempel J, Barton T, Lukas K, Inder TE. Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury. Pediatr Res. 2010 Jan;67(1):102-6. doi: 10.1203/PDR.0b013e3181bf5914.
PubMed 19745782Payne ET, Zhao XY, Frndova H, McBain K, Sharma R, Hutchison JS, Hahn CD. Seizure burden is independently associated with short term outcome in critically ill children. Brain. 2014 May;137(Pt 5):1429-38. doi: 10.1093/brain/awu042. Epub 2014 Mar 4.
PubMed 24595203van Rooij LG, Toet MC, van Huffelen AC, Groenendaal F, Laan W, Zecic A, de Haan TR, van Straaten IL, Vrancken S, van Wezel G, van der Sluijs J, Ter Horst H, Gavilanes D, Laroche S, Naulaers G, de Vries LS. Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial. Pediatrics. 2010 Feb;125(2):e358-66. doi: 10.1542/peds.2009-0136. Epub 2010 Jan 25.
PubMed 20100767
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protecting Brains and Saving Futures - the PBSF Protocol: a Prospective Multicenter and Observational Study on the Use of Telemedicine for Neurocritical Care in High-risk Newborns in Brazil.
- ClinicalTrials.gov ID
- NCT03786497
- Acronym / sponsor ID
- PBSF / PBSF_2020
- Conditions
- Brain Injuries, Congenital Heart Disease, Newborn Morbidity, Intraventricular Hemorrhage, CNS Infection, Neonatal Seizure
- Keywords
- Newborn, Neonatal Neurocritical Care Units, Neonatal Brain Monitoring, Brain Injury, Neuroprotection, Telemedicine, Electroencephalography, Amplitude-Integrated Electroencephalography
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,268 participants (estimated)
- Lead sponsor
- Protecting Brains Saving FuturesUniversity, hospital or other
- Study start
- 1 Jan 2021 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 26 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Multiple neonatal disorders are associated with risks of neurological injury. Thus, management of these infants should involve a coordinated approach to permit early diagnosis with improved clinical care. Such initiative involves the use of standardized protocols, continuous and specialized brain monitoring with electroencephalography (EEG), amplitude integrated EEG (aEEG) and Near Infrared Spectroscopy (NIRS), neuroimaging and training. Brazil is a very large country with disparities in health care assessment; some neonatal intensive care units (NICUs) are not well structured and trained to provide adequate neurocritical care. However, the development and implementation of these neurocritical care units requires high expertise and significant investment of time, manpower and equipment. In order to reduce the existing gap, a unique advanced telemedicine model of neurocritical care called Protecting Brains and Saving Futures (PBSF) protocol was developed and implemented in some Brazilian NICUs.
Methods: A prospective observational cohort study will be conducted in 20 Brazilian NICUs that have adopted the PBSF protocol. All infants receiving the protocol during January 2021 to December 2023 will be eligible. Ethical approval will be obtained from the participating institutions. The primary objective is to describe the use of the PBSF protocol and clinical outcomes, by center and over a 3 years period. The use of the PBSF protocol will be measured by quantification of neuromonitoring, neuroimaging exams and sub-specialties consultation. Clinical outcomes of interest after the protocol implementation are length of hospital stay, detection of EEG seizures during hospitalization, use of anticonvulsants, inotropes, and fluid resuscitation, death before hospital discharge, and referral of patients to high-risk infant follow-up. These data will be also compared between infants with primarily neurologic and primarily clinical diagnosis.
Discussion: The implementation of the PBSF protocol may provide adequate remote neurocritical care in high-risk infants with optimization of clinical management and improved outcomes. Data from this large, prospective, multicenter study are essential to determine whether neonatal neurocritical units can improve outcomes. Finally, it may offer the necessary framework for larger scale implementation and help in the development of studies of remote neuromonitoring.
Detailed description
METHODS Objectives The aim of this multicenter, prospective, cohort study is to describe the use of the PBSF protocol and clinical outcomes, by center and over a 3 years period (2021 to 2023) in the NICUs that have adopted it. We hypothesize that the use of the PBSF protocol will increase over time with improvement of some specific short-term outcomes (see methods below). Results of this study may provide the necessary background information for larger studies and initiatives aiming to protect neonatal brains and save futures.
Study Design and Setting This will be a multicenter, prospective, observational study in a cohort of high-risk neonates treated at 20 different NICU's in Brazil. The intended period of patient recruitment and data collection will be 3 years (January 2021 to December 2023). The study followed the precepts of good clinical practice and was approved by the Research Ethics Committee of the Irmandade da Santa Casa de Misericórdia de São Paulo. In addition, the project has received formal authorization from the Clinical and Administrative Board of each center. When selecting a participant, the principal investigator of the study or one of the co-investigators will contact the parents or guardians and obtain informed consent. All data will be treated anonymously and confidentially, and in no phase of the study any name, image, or data that allows participants identification will be disclosed.
Participants In this cohort study, all the infants admitted to any of the 20 NICUs from birth up to three months of life and receiving the PBSF protocol are eligible. Indications for the use of the protocol are provided on Box 1. Patients with genetic syndromes or malformation incompatible with life, or older than three months old will be excluded. Details on the PBSF protocol are provided in supplemental material. Briefly, the protocol includes provision of equipment and resources, connection between the associated NICU and the remote monitoring center called the Central of Surveillance and Intelligence (CSI), training and teaching of all health care professional team of each NICU, and customized multiparametric recordings of biological signals of each patient monitoring. At the CSI, a team is available 24 hours a day all year around, allowing for case discussions and simplified reports of brain monitoring information on the patient monitor's display every 6 hours.
Variables Population demographics: gender, gestational age at birth, gestational age ≤ 32 weeks and < 37 weeks, Apgar score at 1 min, 5 min and 10 min, birth weight, current weight, inborn or outborn, use of antenatal steroids and magnesium sulfate, type of birth.
Primary diagnosis: seizure, anoxia/mild HIE, moderate or severe HIE/cooling, neurologic abnormalities without specific diagnosis, congenital central nervous system (CNS) anomalies, grade III or IV intraventricular hemorrhage (IVH) or hydrocephalus, periventricular leukomalacia, meningitis, neural tube defects, stroke, cyanotic congenital heart defect (CHD), prematurity, gestational age ≤ 32 weeks, meconium aspiration syndrome, cardiorespiratory instability, necrotizing enterocolitis, metabolic disease, extracorporeal membrane oxygenation (ECMO)/pre-ECMO and any other medical conditions not listed here.
For descriptive analysis of the 2 main outcomes (use of the PBSF protocol and clinical outcomes) patients will be them divided into two groups accordingly to their primary diagnosis: neurological or clinical.
Data sources / measurement Patient demographics, diagnosis and clinical outcomes will be extracted from the medical charts of each patient enrolled and entered in the PBSF database. The use of the PBSF protocol will be measured with the data collected by the CSI center continuously. Details of these recordings are provided on Appendix 2.
Bias To address potential source of bias related to financial availability, the 2 main outcomes of interest will be also adjusted based on the unit primary profile: private, foundation or public.
Study size Based on our current experience, there are an average of 5 patients per month with criteria for neurocritical care on each center, making a total of 3,240 eligible patients during a three years period. Considering a 30% loss due to refusal to consent, non-availability of the research team or missing data, we expect to recruit 2,268 infants from all study centers (around 756 patients per year).
Statistical methods Categorical variables will be analyzed by descriptive statistics and presented as number of valid cases and percentage (%). Numeric variables will be analyzed as mean and standard deviation, median and interquartile ranges, or coefficient intervals. Chi-square test (or Fisher's exact test) will be performed to analyze categorical variables and the Student's t test, or Wilcoxon rank sum test will be used to check for significant differences between the two groups. A p value of <0.05 will be considered statistically significant. The confidence interval considered will be 95%. Analysis of variability (distribution) per site for each variable of the 2 main outcomes will also be performed. ANOVA with post hoc Bonferroni will be used to compare outcomes over time, i.e. between years 1, 2 and 3 and Kaplan Meier curves will be generated to follow the evolution of outcomes over time for the 2 groups of patients: neurologic and clinical.
Results Participants. A flow chart of all eligible and enrolled patients will be produced, and the total number of patients will be reported, overall and per center.
Descriptive data Population demographics: male, n (%); gestational age at birth, weeks, mean (SD); gestational age ≤ 32 wk, n(%); Gestational age < 37 wk, n (%); Apgar score at 1 min, at 5 min, and at 10min, median (IQR); birth weight, grams, mean (SD); current weight, grams, mean (SD); Inborn, n (%); use of antenatal steroids and magnesium sulfate, n (%); Caesarean, n(%).
Primary outcomes:
Use of the PBSF protocol
- Use of aEEG/EEG monitoring
- Duration of aEEG/EEG monitoring
- Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)
- Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)
- Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.
- Number of clinical case discussions and videoconference meetings
Clinical outcomes
- Length of hospital stay
- Number of electroencephalographic seizures during hospitalization
- Use and types of anticonvulsants administered
- Number and types of anticonvulsants prescribed at discharge
- Use and types of inotropes administered during NICU stay
- Use and types of fluid resuscitation administered during NICU stay
- Death before hospital discharge
- Number of patients referred to neurology or neurosurgery
- Number of patients referred to high-risk infant follow-up*
Secondary outcomes:
Use of the PBSF protocol
- Number of remote communications between CSI and local team
- Number of reports issued for aEEG / EEG exams with or without the use of NIRS
- Number of patients who performed Therapeutic Hypothermia
- Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization
- Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay
- Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension
- Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning
- Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 24 Months
Who may qualify
- Ages
- Up to 3 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- This will be a multicenter, prospective, observational study in a cohort of high-risk neonates treated at 20 different Neonatal Intensive Care Units in terciary hospitals in Brazil.
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- Patients with genetic syndromes or malformation incompatible with life, or older than three months old will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Applicability of telemedicine model for monitored infants
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Applicability of telemedicine model for recorded remote monitoring
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Use of aEEG/EEG monitoring
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Duration of aEEG/EEG monitoring
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number of clinical case discussions and videoconference meetings
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Length of hospital stay
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number of electroencephalographic seizures during hospitalization
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Use and types of anticonvulsants administered
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number and types of anticonvulsants prescribed at discharge
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Use and types of inotropes administered during NICU stay
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Use and types of fluid resuscitation administered during NICU stay
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Death before hospital discharge
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number of patients referred to neurology or neurosurgery
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
Number of patients referred to high-risk infant follow-up
Time frame: 3 years period
Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
8 secondary outcomes
Number of remote communications between CSI and local team
Time frame: 3 years period
Number of reports issued for aEEG / EEG exams with or without the use of NIRS
Time frame: 3 years period
Number of patients who performed Therapeutic Hypothermia
Time frame: 3 years period
Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization
Time frame: 3 years period
Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay
Time frame: 3 years period
Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension
Time frame: 3 years period
Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning
Time frame: 3 years period
Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life
Time frame: 3 years period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2020.
- Background: PubMed 20554402Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329-38. doi: 10.1016/j.earlhumdev.2010.05.010. Epub 2010 Jun 16.
- Background: PubMed 15752534Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. doi: 10.1016/S0140-6736(05)71048-5.
- Background: PubMed 16556647Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000. Int J Epidemiol. 2006 Jun;35(3):706-18. doi: 10.1093/ije/dyl043. Epub 2006 Mar 23.
- Background: PubMed 1713544Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991 May;25(2):135-48. doi: 10.1016/0378-3782(91)90191-5.
- BackgroundRobertson CMT. Long-term follow-up of term infants with perinatal asphyxia. In: Stevenson DK, Benitz WE, Sunshine P. Fetal and neonatal brain injury. 3. Ed. New York: Cambridge University; 2003. p.829-58.
- Background: PubMed 20444814de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010 May;95(3):F220-4. doi: 10.1136/adc.2008.148205.
- Background: PubMed 16113154Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F380-7. doi: 10.1136/adc.2004.067520.
- Background: PubMed 24366461Blencowe H, Lee AC, Cousens S, Bahalim A, Narwal R, Zhong N, Chou D, Say L, Modi N, Katz J, Vos T, Marlow N, Lawn JE. Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatr Res. 2013 Dec;74 Suppl 1(Suppl 1):17-34. doi: 10.1038/pr.2013.204.
- Background: PubMed 17067863Hellstrom-Westas L, Rosen I. Continuous brain-function monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med. 2006 Dec;11(6):503-11. doi: 10.1016/j.siny.2006.07.011. Epub 2006 Oct 24.
- BackgroundHellström-Westas L, Rosén I, de Vries LS, Greisen G. Amplitude-integrated EEG Classification and Interpretation in Preterm and Term Infants. NeoReviews. 2006;7(2):e76-87.
- Background: PubMed 18519484Shah DK, Mackay MT, Lavery S, Watson S, Harvey AS, Zempel J, Mathur A, Inder TE. Accuracy of bedside electroencephalographic monitoring in comparison with simultaneous continuous conventional electroencephalography for seizure detection in term infants. Pediatrics. 2008 Jun;121(6):1146-54. doi: 10.1542/peds.2007-1839.
- Background: PubMed 23725740Mastrangelo M, Fiocchi I, Fontana P, Gorgone G, Lista G, Belcastro V. Acute neonatal encephalopathy and seizures recurrence: a combined aEEG/EEG study. Seizure. 2013 Nov;22(9):703-7. doi: 10.1016/j.seizure.2013.05.006. Epub 2013 May 29.
- 25\. World Health Organization. A health telematics policy in support of WHO's Health-for-All Strategy for Global Health Development. Geneva (Switzerland); 1998.Link provided by the sponsor.
- 26\. World Health Organization. Telemedicine: Opportunities and Development in Member States: Report on the second global survey on eHealth. Geneva (Switzerland); 2010.Link provided by the sponsor.
- 30\. Ministério da Saúde. DATASUS. \[online\] Tabnet. \[accessed on Jan 10th 2018\]Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guilherme M Sant'Anna, PhD study director
McGill University Health Centre/Research Institute of the McGill University Health Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Injuries and Congenital Heart Disease, run by Protecting Brains Saving Futures at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gabriel FT Variane, MD (5511996243520, gabriel.variane@pbsf.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Applicability of telemedicine model for monitored infants (time frame: 3 years period). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03786497, which also lists 83 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2020; AzTrials last refreshed its copy on 26 Oct 2026.