Protecting Brains and Saving Futures - the PBSF Protocol

Congenital Heart Disease Clinical Trial

— PBSF  

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03786497
• Other study ID #: PBSF_2020
• Status: Not yet recruiting
• Start date: January 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: November 2020
• Source: Protecting Brains Saving Futures
• Contact: Gabriel FT Variane, MD
• Phone: 5511996243520
• Email: gabriel.variane[@]pbsf.com.br
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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. 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.

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

1. Use of aEEG/EEG monitoring

2. Duration of aEEG/EEG monitoring

3. Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)

4. Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)

5. Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.

6. Number of clinical case discussions and videoconference meetings

Clinical outcomes

1. Length of hospital stay

2. Number of electroencephalographic seizures during hospitalization

3. Use and types of anticonvulsants administered

4. Number and types of anticonvulsants prescribed at discharge

5. Use and types of inotropes administered during NICU stay

6. Use and types of fluid resuscitation administered during NICU stay

7. Death before hospital discharge

8. Number of patients referred to neurology or neurosurgery

9. Number of patients referred to high-risk infant follow-up*

Secondary outcomes:

Use of the PBSF protocol

1. Number of remote communications between CSI and local team

2. Number of reports issued for aEEG / EEG exams with or without the use of NIRS

3. Number of patients who performed Therapeutic Hypothermia

4. 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

5. Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay

6. Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension

7. Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning

8. Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2268
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 3 Months

Eligibility

• Inclusion criteria:

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. Following are the indications for use of the PBSF protocol in the participating centers

1. Extreme prematurity

2. Peri-intraventricular Hemorrhage

3. Hypoxic-ischemic encephalopathy (mild, moderate or severe)

4. Congenital heart disease

5. Neonatal stroke

6. Congenital infections

7. Nosocomial infections

8. Inborn errors of metabolism

9. Severe hemodynamic/ventilatory instability

10. Seizures

11. Brain malformations

12. CNS infection

13. ECMO

• Exclusion criteria:

Patients with genetic syndromes or malformation incompatible with life, or older than three months old will be excluded.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Injuries
• Brain Ischemia
• Brain Malformation
• CNS Infection
• Communicable Diseases
• Congenital Heart Disease
• Congenital Infection
• Cross Infection
• Extracorporeal Membrane Oxygenation Complication
• Extreme Prematurity
• Heart Diseases
• Hemodynamic Instability
• Hemorrhage
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Inborn Errors of Metabolism
• Infection
• Intraventricular Hemorrhage
• Metabolism, Inborn Errors
• Neonatal Death
• Neonatal Seizure
• Neonatal Stroke
• Newborn Morbidity
• Nosocomial Infection
• Perinatal Death
• Respiratory Complication
• Seizures

Locations

Country	Name	City	State
Brazil	Irmandade da Santa Casa de Misericórdia de São Paulo	São Paulo	SP
Brazil	Protecting Brains and Saving Futures - PBSF	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Protecting Brains Saving Futures

Country where clinical trial is conducted

Brazil, 

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* Note: There are 82 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Primary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period
Secondary	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).	3 years period

External Links

•   25. World Health Organization. A health telematics policy in support of WHO's Health-for-All Strategy for Global Health Development. Geneva (Switzerland); 1998.
•   26. World Health Organization. Telemedicine: Opportunities and Development in Member States: Report on the second global survey on eHealth. Geneva (Switzerland); 2010.
•   30. Ministério da Saúde. DATASUS. [online] Tabnet. [accessed on Jan 10th 2018]
•   34. World Health Organization. [online] The World Health Report 2005 - make every mother and child count; 2005. [accessed on Oct 14th 2019]