Paediatric Inflammatory Multisystem Syndrome During COVID-19 Pandemic

February 8, 2022 updated by: Anglia Ruskin University

Investigating Cytokine Storm Biomarkers in Children Presenting to Acute Paediatric Services (Non-intensive Care) With Paediatric Inflammatory Multisystem Syndrome During the Covid-19 Pandemic. An Observation Study

During the COVID-19 pandemic, a small minority of children have been presenting to acute paediatric services with a new syndrome, Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-Cov-2 (PIMS-TS). Children with PIMS-TS present with symptoms of inflammation caused by the immune system going into overdrive - this is likely to be in response to the virus. More severe cases involve inflammation and damage to the heart.

The focus of this project is to identify children with milder forms of PIMS-TS who are at risk of progression to more severe disease. Being able to predict the disease course of PIMS-TS at an early stage is important as it will allow clinicians to decide which patients should be treated with immunosuppressants, which have been shown to reduce the severity of the illness but have side effects.

Early data suggests that children with PIMS-TS have elevated biomarkers associated with an over-reaction of the body's immune system (also known as a 'cytokine storm') reaction. This study will explore whether children presenting with milder PIMS-TS have elevated 'cytokine storm' blood profiles and whether these profiles differ between children who continue to have a mild disease course compared to those who develop severe disease.

Study Overview

Status

Completed

Conditions

Detailed Description

During the COVID-19 pandemic a minority of children have presented to acute services with clinical features of a new syndrome known as Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-Cov-2 (PIMS-TS). This high inflammatory state, likely triggered by the virus, has overlapping features of Kawasaki's and Toxic Shock Syndrome.

The focus of this study is to identify which children presenting with mild PIMS-TS symptoms will go on to develop severe disease requiring intensive care unit (ICU) admission. This is important as data suggests that early aggressive treatment with immunosuppression can lead to a relatively quick resolution in symptoms. The results of this study could allow clinicians to be selective in treating patients in whom the benefits of treatment outweigh the risks.

Early data suggests a 'cytokine storm' is involved in the PIMS-TS disease process. This proposed observational study will investigate whether children presenting to the non-ICU setting with features of PIMS-TS have raised cytokine storm biomarkers and whether these may be used to predict which children go onto develop severe disease.

The proposed study will include up to 15 hospitals across East of England. NHS clinical care teams will identify patients meeting the inclusion criteria and upload anonymised data into a secure web-based study database. Data will be retrieved for retrospective cases from 1st March 2020 and prospective data entered up until September 2021.

One hundred children presenting to acute (non-ICU) paediatric services with symptoms of PIMS-TS during the study period will be included.

The primary objective of the study is to describe the 'cytokine storm' biomarker profiles of children aged between 3 months to 16 years presenting with PIMS-TS to the non-ICU setting, focussing on those biomarkers which are readily accessible to district general hospitals (Pro-Beta Natriuretic peptide [BNP], ferritin, and CRP).

The secondary aims of the study are to:

  1. Compare cytokine storm biomarker profiles of children who have a mild disease course to those who develop severe disease to identify whether there are any differences between these groups
  2. Evaluate the association between cytokine storm biomarker profiles and severe events
  3. Compare i) demographic characteristics (including pre-existing disease), and ii) other routine clinical investigations of children who have a mild disease course and those who develop severe disease to identify any differences between these 2 groups
  4. Evaluate the association between vaccination status and disease severity
  5. Compare cytokine storm biomarker profiles of children testing positive and those testing negative for SARS-CoV-2 via PCR on 2x nasopharyngeal swabs to identify any differences between these 2 groups.

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

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

Study Locations

  • United Kingdom
    • Essex
      • Chelmsford, Essex, United Kingdom, CM1 7ET
        • Mid Essex Hospital Trust
      • Colchester, Essex, United Kingdom, CO4 5JL
        • East Suffolk and North Essex NHS Foundation Trust
      • Harlow, Essex, United Kingdom, CM20 1QX
        • The Princess Alexandra Hospital NHS Trust
    • Norfolk
      • Great Yarmouth, Norfolk, United Kingdom, NR31 6LA
        • James Paget University Hospitals NHS Foundation Trust
      • Norwich, Norfolk, United Kingdom, NR4 7UY
        • Norfolk and Norwich University Hospitals NHS Foundation Trust
    • Suffolk
      • Ipswich, Suffolk, United Kingdom, IP4 5PD
        • East Suffolk and North Essex Foundation Trust

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

3 months to 16 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children (aged 3 months to ≤ 16 years) presenting to acute paediatric services (non-ICU) with symptoms of PIMS during the period of the COVID-19 pandemic

Description

Inclusion Criteria:

  • Within the age range of 3 months to ≤16 years
  • Presenting clinically to non-ICU paediatric acute services at hospitals in the East of England region with symptoms suggestive of PIMS (e.g. incomplete Kawasaki's disease/Toxic Shock Syndrome) i.e. having: persistent fever (>38.0oC for 5 or more days) AND high CRP (>80) AND with one or more of additional features listed in Appendix 1 of the RCPCH document 'Guidance: paediatric multisystem inflammatory syndrome temporarily associated with COVID-19'
  • Having either a positive or negative SARS-Cov-2 PCR test

Exclusion Criteria:

  • Aged below 3 months old or above 16 years old
  • Confirmation of any microbial cause other than SARS-Cov-2 (including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus). Determination of such microbial causes is by routine testing i.e. blood culture; pneumococcal, meningococcal, group A strep, staph aureus blood PCR; ASOT; EBV, CMV, adenovirus, enterovirus PCR on blood; urine and stool culture; throat swab culture; stool virology.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood biomarker associated with a cytokine storm - Pro-Beta Natriuretic Peptide (measured in pg/mL).
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Pro-Beta Natriuretic Peptide (BNP) measured as part of routine clinical care. NHS care teams will upload anonymised routine clinical measurements into a secure study database.
From date of admission to date of discharge from hospital assessed up to 18 months
Blood biomarker associated with a cytokine storm - Ferritin (measured in µg/L)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Ferritin measured as part of routine clinical care. NHS care teams will upload anonymised routine clinical measurements into a secure study database.
From date of admission to date of discharge from hospital assessed up to 18 months
Blood Biomarker associated with a cytokine storm - C-Reactive Protein (measured in mg/L)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
C-Reactive Protein measured as part of routine clinical care. NHS care teams will upload anonymised routine clinical measurements into a secure study database.
From date of admission to date of discharge from hospital assessed up to 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demographic characteristics including age, sex, ethnicity and pre-existing morbidities
Time Frame: At admission to hospital
Information collected as part of routine clinical care. NHS clinical care teams will upload anonymous data into a secure study database.
At admission to hospital
Hospital stay data
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Information collected as part of routine clinical care. NHS clinical care teams will upload anonymous data into a secure study database.
From date of admission to date of discharge from hospital assessed up to 18 months
Cytokine storm biomarker measured in mg/L (CRP)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Cytokine storm biomarkers measured in pg/mL (pro-beta natriuretic peptide, IL-6, IFN-gamma, IL-10, TNF-alpha)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Full blood count measures in 10^9/L (white cell count - neutrophil and lymphocyte count and platelet)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Full blood count measures in L/L (haematocrit)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Haemoglobin in g/L or g/dL (measured as part of full blood count and blood gas analysis)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Blood gas analysis measured in KPa (pCO2, pO2)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Blood gas analysis measured in mmol/l (glucose, lactate, Na, K and Cl)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Blood gas analysis measured in mmol/l or mEq/L (HCO3, BE)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Liver function tests measured in g/L (protein, albumin, globulin)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Liver function tests measured in U/L (ALP/ALT)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Liver function tests measured in µmol/L (bilirubin)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Troponin measured in ng/ml or ng/L
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
vitamin D measured in nmol/L
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Amylase, CK, LDH measured in U/L
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Glucose and triglycerides measured in mmol/L
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Urea and electrolytes measured in mmol/L (Na, K, urea)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Urea and electrolytes measured in µmol/L (creatinine)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
ferritin measured in µg/L
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
fibrinogen measured in g/L
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
D-dimer measured in ng/ml
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
PT and APTT measured in seconds
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
INR as a ratio (Patient PT/Control PT)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Acute Kidney Injury graded as no AKI or stage of AKI (1-3)
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Positive or negative COVID-19 antibody test
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Clinical investigations (blood biomarkers) collected as part of routine clinical care
From date of admission to date of discharge from hospital assessed up to 18 months
Presence or absence of clinical conditions as assessed by ECG/echocardiography
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Conditions will include: myocarditis, valvulitis, pericardial effusion, coronary artery dilation, or other conditions.
From date of admission to date of discharge from hospital assessed up to 18 months
Presence or absence of clinical conditions as assessed by chest x-ray/chest CT
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Conditions will include: presence of patchy symmetrical infiltrates, pleural effusion, coronary artery abnormalities (CT with contrast) or other conditions.
From date of admission to date of discharge from hospital assessed up to 18 months
Presence or absence of clinical conditions as assessed by abdominal ultrasound
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Conditions will include: colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly or other conditions.
From date of admission to date of discharge from hospital assessed up to 18 months
Proteinuria as assessed by urinalysis graded as no protein, protein ++ or protein +++
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
From date of admission to date of discharge from hospital assessed up to 18 months
Positive or negative COVID swab result as assessed by PCR
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
From date of admission to date of discharge from hospital assessed up to 18 months
Positive or negative NPA or throat swab result for respiratory panel as assessed by PCR
Time Frame: From date of admission to date of discharge from hospital assessed up to 18 months
Including: pneumococcal, meningococcal, Group A Strep, Staph Aureus, EBV, CMV, Andenovirus, Enterovirus
From date of admission to date of discharge from hospital assessed up to 18 months
Vaccination status
Time Frame: At admission to hospital
Information collected as part of routine clinical care. NHS clinical care teams will upload anonymous data into a secure study database.
At admission to hospital

Collaborators and Investigators

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

Sponsor

Anglia Ruskin University

Investigators

  • Principal Investigator: Jo-Anne Johnson, MRCPCH, PhD, Anglia Ruskin University

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)

June 22, 2021

Primary Completion (ACTUAL)

December 31, 2021

Study Completion (ACTUAL)

December 31, 2021

Study Registration Dates

First Submitted

December 11, 2020

First Submitted That Met QC Criteria

February 18, 2021

First Posted (ACTUAL)

February 21, 2021

Study Record Updates

Last Update Posted (ACTUAL)

February 9, 2022

Last Update Submitted That Met QC Criteria

February 8, 2022

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19/20/048

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 Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-Cov-2

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ukraine

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe