Clinical trial NCT04330261: Clinical Characteristics and Outcomes of Pediatric COVID-19
Official title: Clinical Characteristics and Outcomes of Children Potentially Infected by Severe Acute Respiratory Distress Syndrome (SARS)-CoV-2 Presenting to Pediatric Emergency Departments
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
SARS-CoV-2 Infection
Pediatric ALL
Pneumonia, Viral
Pandemic Response
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2020-04-01
Enrollment: 10610
Sex: ALL
Minimum age (years): 0
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: All children presenting to a participating ED who are screened (i.e. tested) for SARS-CoV-2 during the duration of the study. Children will be mainly from urban areas across Canada, United States of America, Italy, Spain, Australia, New Zealand, Argentina, Singapore, and other countries.

Brief summary: Rationale: The clinical manifestations of SARS-CoV-2 infection in children are poorly characterized. Preliminary findings indicate that they may be atypical. There is a need to identify the spectrum of clinical presentations, predictors of severe disease (COVID-19) outcomes, and successful treatment strategies in this population.

Goals:

Primary - Describe and compare characteristics of confirmed SARS-CoV-2 infected children with symptomatic test-negative children.

Secondary - 1) Describe and compare confirmed SARS-CoV-2 infected children with mild versus severe COVID-19 outcomes; 2) Describe healthcare resource utilization for, and outcomes of, screening and care of pediatric COVID-19 internationally, alongside regional public health policy changes.

Methods: This prospective observational study will occur in 50 emergency departments across 11 countries. We will enroll 12,500 children who meet institutional screening guidelines and undergo SARS-CoV-2 testing. Data collection focuses on epidemiological risk factors, demographics, signs, symptoms, interventions, laboratory testing, imaging, and outcomes. Collection will occur at enrollment, 14 days, and 90 days.

Timeline: Recruitment will last for 12 months (worst-case model) and will begin within 7-14 days of funding notification after ongoing expedited review of ethics and data sharing agreements.

Impact: Results will be shared in real-time with key policymakers, enabling rapid evidence-based adaptations to pediatric case screening and management.

Detailed description: Pediatric COVID-19: The characteristics of pediatric 2019 novel coronavirus disease (COVID-19) are not yet well understood. Preliminary findings indicate that atypical presentations of COVID-19 occur in children. Thus, there is an urgent need to identify risk factors for pediatric COVID-19 infection, the range of clinical manifestations, predictors of severe outcomes, and successful treatment strategies.

Objectives: Primary: To contribute to the optimization of medical countermeasures to pediatric COVID-19 through describing and comparing the clinical characteristics of SARS-CoV-2 infected children (i.e. test positive) with children who were screened for SARS-CoV-2 but tested negative. We will also describe and compare SARS-CoV-2 infected children with mild versus those with severe outcomes. This study will also describe the health care resources utilized for screening, isolation, and care of pediatric COVID-19, examined alongside relevant public health policies.

Methods: This is a two-year prospective observational study that will take place at 50 EDs across 19 countries. We will enroll children (\<18 years old) presenting to participating study EDs who meet institutional screening guidelines and undergo testing for COVID-19. Data collection is aligned with WHO templates and focuses on epidemiological factors, demographics, signs, symptoms, exposures, interventions, and test results. Collection will occur at the time of enrolment, during the course of illness, at hospital discharge (if admitted), and at two weeks and three months following enrolment. Over a period of 18 months (starting March 31st, 2020) we aim to enroll and complete follow-up for a total of 5000 children with screened for suspected SARS-CoV-2 infection. Data will be entered into a centralized database, and analyzed using simple and multiple ordinal logistic regression models. Data will be interpreted alongside detailed, prospectively collected, information on the changes to case isolation, screening, and management policies that occur throughout the epidemic in each institution and study region.

Feasibility: The Pediatric Emergency Research Networks (PERN) represents the largest international acute pediatric care collaboration in the world, including more than 200 hospitals across 35 countries. Currently, PERN is carrying out the PERN-Pneumonia prospective cohort study, designed to identify predictors of severe pneumonia at 70 hospitals around the globe, including at eight Canadian pediatric emergency departments (ED). This study will build onto the PERN-Pneumonia study infrastructure (e.g. ethics approvals, data sharing agreements, research teams) in order to facilitate a unique, rapid, and global response to the COVID-19 epidemic. Feasibility is enhanced by our design - we will not interfere with the existing COVID-19 screening and management procedures in-place in study EDs; we will not collect any biological specimens, and will not prescribe any interventions.

Project Team: This international multidisciplinary team includes pediatric emergency medicine and infectious disease clinicians, epidemiologists, statisticians, and public health leaders from around the globe. Team members have led many landmark trials in pediatric emergency medicine, and lead large pediatric research networks and studies including the PERN-Pneumonia study. They also came together to study the H1N1 pandemic and identified predictors of severe outcomes. Team members also have expertise in pediatric lower respiratory tract infections, biostatistics, and epidemiology (including the CDC lead on the MERS-CoV outbreak). This study team also includes the Public Health Agency of Canada's senior medical/technical expert on COVID-19.

Impact of the research: The results of this study, which will be shared in real-time with appropriate national and international authorities, will enable policymakers to make rapid evidence-based adaptations to case screening and management procedures that will then allow for the earlier identification of children likely to have confirmed infection with COVID-19 as well as to prioritize those children likely to have severe outcomes. Finally, the establishment of this global multi-site study will be the first trial of a rapid PERN networks response to a pandemic novel respiratory virus, which, applying lessons-learned, can be urgently reactivated for future public health emergencies.

Eligibility criteria: Inclusion Criteria:

1. \< 18 years-old, and
2. Present to a participating ED for care, and
3. Undergo SARS-CoV-2 testing.

Exclusion Criteria:

1) Refusal to participate (no informed consent)

Primary outcomes:
measure: Clinical characteristics of children with SARS-CoV-2
timeFrame: 18 months
measure: Factors associated with severe COVID-19 outcomes
timeFrame: 18 months
Secondary outcomes:
measure: Health care resource utilization for COVID-19 patient management
timeFrame: 18 months
measure: Sensitivity and specificity of COVID-19 case screening policies
timeFrame: 18 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary/Alberta Children's Hospital
state: Alberta
Study officials:
affiliation: University of Calgary
name: Stephen Freedman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Funk AL, Florin TA, Dalziel SR, Mintegi S, Salvadori MI, Tancredi DJ, Neuman MI, Payne DC, Plint AC, Klassen TP, Malley R, Ambroggio L, Kim K, Kuppermann N, Freedman SB. Prospective cohort study of children with suspected SARS-CoV-2 infection presenting to paediatric emergency departments: a Paediatric Emergency Research Networks (PERN) Study Protocol. BMJ Open. 2021 Jan 15;11(1):e042121. doi: 10.1136/bmjopen-2020-042121.