Clinical trial NCT06938009: Dutch Registry of Pediatric Cardiac Arrest
Official title: Pediatric Resuscitation Neuroprognostication and Outcomes Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiac Arrest (CA)
Pediatric ALL
Keywords: Pediatric cardiac arrest
Neuroprognostication
Long-term outcomes
Observational registry
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Amsterdam UMC
name: Radboud University Medical Center
name: UMCG
name: Maastricht University Medical Center
name: UMC Utrecht
name: Zoll Medical Corporation
name: Stichting Vermeer14
name: Leiden University Medical Center
First posted: 2025-04-22
Enrollment: 500
Sex: ALL
Minimum age (years): 24
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric patients under 18 years of age who experienced a cardiac arrest, either in-hospital or out-of-hospital, in the Netherlands. Eligible patients must have received chest compressions for at least one minute and been treated by emergency medical services or admitted to one of seven participating Dutch academic pediatric hospitals. Neonates under 24 hours old and NICU arrests are excluded.

Brief summary: The goal of this observational study is to understand the long-term outcomes of children in the Netherlands who experience cardiac arrest, either in or outside of the hospital. The main questions it aims to answer are:

What are the survival rates and neurological outcomes in children after cardiac arrest?

What types of emergency and post-resuscitation care are provided, and how do they impact long-term recovery?

How do children and their families function over time after the event?

Researchers will analyze data from routine medical records and follow patients through standard outpatient visits. No extra procedures will be required beyond normal care. For those who survive to hospital discharge, additional follow-up data will be collected with consent.

Participants will:

Be children under 18 years old who have had a cardiac arrest and were treated in one of the seven participating academic hospitals

Have their routine medical care data collected anonymously

Be invited (if surviving) for follow-up visits at 3, 12, and 24 months post-arrest and at specific ages (5, 8, 12, and 17 years) to assess physical and psychological recovery

Detailed description: The PROGNOSE study (Pediatric Resuscitation Neuroprognostication and Outcomes Registry) is a prospective, multicenter, observational patient registry established to improve understanding of short- and long-term outcomes following pediatric cardiac arrest (CA) in the Netherlands. The study focuses on both out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA) in children under 18 years of age.

Given the rarity yet severity of pediatric CA, the registry aims to collect a large dataset to identify patterns in care, outcomes, and recovery trajectories to ultimately improve treatment strategies and prognosis. The study is considered non-WMO (not subject to the Dutch Medical Research Involving Human Subjects Act), as it involves no additional interventions beyond standard clinical care.

Registry Objectives and Scope The primary objective is to evaluate diagnostic practices and long-term functional and neuropsychological outcomes in pediatric patients post-cardiac arrest. Key secondary objectives include determining the incidence and etiology of pediatric CA in the Netherlands, analyzing survival to discharge, and characterizing post-Return of Circulation (ROC) care.

Data will be collected longitudinally during standard outpatient follow-up visits at specified intervals (3, 12, and 24 months post-arrest; and at the ages of 5, 8, 12, and 17 years, depending on the age at CA event). No study-specific interventions will be performed.

Data Collection and Source Verification

All data collected in this registry will be sourced from routine clinical care and medical records from seven Dutch academic (pediatric) hospitals. Data will be abstracted from:

Emergency services records

Inpatient hospital and ICU documentation

Follow-up outpatient clinic assessments

Neuropsychological and functional evaluations using validated tools (e.g., PCPC, POPC, FSS)

The data will be pseudo-anonymized using unique study IDs. Only site-specific investigators will have access to the link between study ID and patient identity.

Quality Assurance and Monitoring

A robust quality assurance framework has been put in place to ensure data integrity, including:

Data validation procedures: Data entries will be checked against predefined rules for logic, consistency, and range validation in the electronic data capture (EDC) system (Castor EDC).

Source data verification (SDV): Periodic audits by local site PIs will compare registry entries against source data (e.g., EHRs) for completeness and accuracy.

Site monitoring: The coordinating center (Erasmus MC) will provide oversight and perform routine cross-site reviews to ensure harmonized data collection.

Data dictionary: A detailed data dictionary defines all collected variables, including their source, coding schemes (e.g., ICD, MedDRA where applicable), and interpretation ranges.

Standard Operating Procedures (SOPs)

Standard operating procedures have been established to guide the entire registry lifecycle, including:

Site initiation and training

Patient screening and enrollment processes

Data entry and validation procedures

Procedures for obtaining (delayed) informed consent at follow-up

Change management and version control of registry forms

Procedures for data sharing and publication

Statistical Analysis Plan Given its quality improvement nature, no formal sample size calculation was performed. Instead, the registry aims to enroll all eligible pediatric CA cases nationwide, allowing the creation of a comprehensive, hypothesis-generating dataset.

Descriptive statistics will summarize demographics, event characteristics, interventions, and outcomes.

Longitudinal analysis of neuropsychological function and functional status will be performed using repeated-measures ANOVA or mixed-effects modeling.

Comparative statistics (e.g., logistic regression) will be used to identify predictors of survival and favorable neurological outcome. Covariates will be selected based on literature and tested for collinearity. Multivariate models will report odds ratios with 95% confidence intervals.

Missing data will be addressed using appropriate imputation techniques, depending on the mechanism of missingness (e.g., multiple imputation for random missing data).

Plan for Missing Data

To manage incomplete records and potential attrition in follow-up:

All missing values will be coded according to reason (e.g., not applicable, patient deceased, declined follow-up).

Patterns of missingness will be explored. If data are missing at random, multiple imputation may be used in analysis.

Data collection tools prompt required fields and flag missing values to reduce omissions during entry.

Informed Consent and Ethics Due to the emergent nature of CA and the high mortality rate, an exception from consent procedure is employed for initial data collection. For survivors, informed consent is sought at follow-up outpatient visits, as part of standard care. Data are de-identified and used solely for research purposes. No images or human materials are collected.

The study complies with the General Data Protection Regulation (GDPR), the Dutch "Code Goed Gedrag," and the Declaration of Helsinki.

Data Storage and Access Pseudo-anonymized data are stored securely in Castor EDC, managed by Erasmus MC.

Each center has access only to its own data.

A Data Transfer Agreement (DTA) governs anonymized data sharing for multicenter publications.

Data will not be shared outside the EU.

No end date is set for the registry; it will remain open for ongoing data entry and hypothesis generation.

Dissemination Plan Findings from the registry will be disseminated through peer-reviewed publications, with a goal of generating multicenter analyses and contributing to national and international guideline development. A first multicenter manuscript is expected within approximately five years from the start of the registry.

Eligibility criteria: Inclusion Criteria:

* Pediatric patients under the age of 18
* Experienced in-hospital or out-of-hospital cardiac arrest in the Netherlands
* Attended by emergency medical services or admitted to one of the seven participating Dutch academic pediatric hospitals
* Cardiac arrest defined as absence of palpable pulse or need for chest compressions lasting ≥1 minute
* Arrest managed under European Resuscitation Council guidelines (BLS/APLS)

Exclusion Criteria:

* Cardiac arrest occurring in neonates younger than 24 hours of age
* Cardiac arrest occurring in a neonatal intensive care unit (NICU) setting

Primary outcomes:
measure: Long-term Neurological Outcome (PCPC)
timeFrame: At 3, 12, and 24 months post-cardiac arrest; and at ages 8, 12, and 17 years, depending on age at event
measure: Long-term Neurological Outcome (POPC)
timeFrame: At 3, 12, and 24 months post-cardiac arrest; and at ages 8, 12, and 17 years, depending on age at event
measure: Long-term Neurological Outcome (FSS)
timeFrame: At 3, 12, and 24 months post-cardiac arrest; and at ages 8, 12, and 17 years, depending on age at event
measure: Neuropsychological Functioning in Pediatric Survivors (composite IQ)
timeFrame: At 12 and 24 months after cardiac arrest
measure: Neuropsychological Functioning in Pediatric Survivors (BRIEF-2 or BRIEF-P)
timeFrame: At 12 and 24 months after cardiac arrest
measure: Neuropsychological Functioning in Pediatric Survivors (CBCL)
timeFrame: At 12 and 24 months after cardiac arrest
measure: Neuropsychological Functioning in Pediatric Survivors (PedsQL)
timeFrame: At 12 and 24 months after cardiac arrest
Secondary outcomes:
measure: Incidence and Cause of Cardiac Arrest
timeFrame: At the time of in-hospital or out-of-hospital cardiac arrest, during initial hospital evaluation
measure: Pre-hospital Interventions Performed (Composite)
timeFrame: At time of cardiac arrest event, as documented during emergency response and initial hospital admission
measure: Duration of Cardiopulmonary Resuscitation (CPR)
timeFrame: At the time of the cardiac arrest event, as documented during emergency medical response and initial hospital admission.
measure: Return of Circulation (ROC)
timeFrame: Time Frame: During initial hospital admission following cardiac arrest
measure: Survival to Hospital Discharge
timeFrame: Time Frame: During initial hospital admission following cardiac arrest
measure: In-Hospital Mortality
timeFrame: During initial hospital admission following cardiac arrest
measure: Brain Magnetic Resonance Imaging (MRI) Findings
timeFrame: During initial hospital admission following cardiac arrest. Within 7 days after cardiac arrest.
measure: Electroencephalography (EEG) Background Assessment
timeFrame: At 24 hours after return of circulation following cardiac arrest.
measure: Blood Biomarker Analysis
timeFrame: Within the first 72 hours after cardiac arrest
measure: Family/Caregiver Outcomes PedsQL-FIM
timeFrame: At 3, 12, and 24 months after the cardiac arrest event
measure: Family/Caregiver Outcomes HADS
timeFrame: At 3, 12, and 24 months after the cardiac arrest event
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud umc
state: Gelderland
city: Maastricht
country: Netherlands
facility: MUMC
state: Limburg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
city: Leiden
country: Netherlands
facility: LUMC
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: UMCG
city: Utrecht
country: Netherlands
facility: UMCU
Study officials:
affiliation: Erasmus Medical Center
name: Corinne Buysse, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: