Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Paediatric Inflammatory Multisystem Syndrome During COVID-19 Pandemic

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04761913
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : July 22, 2021
Sponsor:
Information provided by (Responsible Party):
Anglia Ruskin University

Brief Summary:

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.


Condition or disease
Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-Cov-2

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: 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
Actual Study Start Date : June 22, 2021
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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.

  28. 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.

  29. 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.

  30. 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 ]
  31. 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 ]
  32. 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

  33. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Months to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04761913


Contacts
Layout table for location contacts
Contact: Jo-Anne Johnson, MRCPCH, PhD 07789 932495 jo-anne.johnson@aru.ac.uk
Contact: Anglia Ruskin Clinical Trials Unit arctu@aru.ac.uk

Locations
Layout table for location information
United Kingdom
Mid Essex Hospital Trust Recruiting
Chelmsford, Essex, United Kingdom, CM1 7ET
Contact: Manas Datta, FRCPCH       manas.datta@meht.nhs.uk   
East Suffolk and north Essex NHS Foundation Trust Recruiting
Colchester, Essex, United Kingdom, CO4 5JL
Contact: Jo-Anne Johnson, PhD, MRCPCH       Jo-Anne.Johnson@aru.ac.uk   
The Princess Alexandra Hospital NHS Trust Recruiting
Harlow, Essex, United Kingdom, CM20 1QX
Contact: Edward Haworth, MSc, MRCPCH       Edward.Haworth2@nhs.net   
James Paget University Hospitals NHS Foundation Trust Recruiting
Great Yarmouth, Norfolk, United Kingdom, NR31 6LA
Contact: Narasimha R Kollipara, MBBS, MRCPCH       Narasimhrao.kollipara@jpaget.nhs.uk   
Norfolk and Norwich University Hospitals NHS Foundation Trust Recruiting
Norwich, Norfolk, United Kingdom, NR4 7UY
Contact: Catherine Thomas, MRCPCH       catherine.thomas@nnuh.nhs.uk   
East Suffolk and North Essex Foundation Trust Recruiting
Ipswich, Suffolk, United Kingdom, IP4 5PD
Contact: Jo-Anne F Johnson, PhD, MRCPCH       Jo-Anne.Johnson@aru.ac.uk   
Sponsors and Collaborators
Anglia Ruskin University
Investigators
Layout table for investigator information
Principal Investigator: Jo-Anne Johnson, MRCPCH, PhD Anglia Ruskin University
Layout table for additonal information
Responsible Party: Anglia Ruskin University
ClinicalTrials.gov Identifier: NCT04761913    
Other Study ID Numbers: 19/20/048
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: July 22, 2021
Last Verified: July 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anglia Ruskin University:
cytokine storm
biomarkers
PIMS-TS
children
COVID-19
Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Disease
Pathologic Processes