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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 6
- 主要终点
- Blood biomarker associated with a cytokine storm - Ferritin (measured in µg/L)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 3 Months 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Blood biomarker associated with a cytokine storm - Ferritin (measured in µg/L)
时间窗: 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.
Blood biomarker associated with a cytokine storm - Pro-Beta Natriuretic Peptide (measured in pg/mL).
时间窗: 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.
Blood Biomarker associated with a cytokine storm - C-Reactive Protein (measured in mg/L)
时间窗: 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.
次要结局
- Full blood count measures in 10^9/L (white cell count - neutrophil and lymphocyte count and platelet)(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)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Blood gas analysis measured in KPa (pCO2, pO2)(From date of admission to date of discharge from hospital assessed up to 18 months)
- D-dimer measured in ng/ml(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(From date of admission to date of discharge from hospital assessed up to 18 months)
- Cytokine storm biomarker measured in mg/L (CRP)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Urea and electrolytes measured in µmol/L (creatinine)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Hospital stay data(From date of admission to date of discharge from hospital assessed up to 18 months)
- Full blood count measures in L/L (haematocrit)(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)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Liver function tests measured in U/L (ALP/ALT)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Liver function tests measured in µmol/L (bilirubin)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Amylase, CK, LDH measured in U/L(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)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Positive or negative COVID-19 antibody test(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(From date of admission to date of discharge from hospital assessed up to 18 months)
- Troponin measured in ng/ml or ng/L(From date of admission to date of discharge from hospital assessed up to 18 months)
- vitamin D measured in nmol/L(From date of admission to date of discharge from hospital assessed up to 18 months)
- ferritin measured in µg/L(From date of admission to date of discharge from hospital assessed up to 18 months)
- fibrinogen measured in g/L(From date of admission to date of discharge from hospital assessed up to 18 months)
- PT and APTT measured in seconds(From date of admission to date of discharge from hospital assessed up to 18 months)
- Demographic characteristics including age, sex, ethnicity and pre-existing morbidities(At admission to hospital)
- Cytokine storm biomarkers measured in pg/mL (pro-beta natriuretic peptide, IL-6, IFN-gamma, IL-10, TNF-alpha)(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)(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)(From date of admission to date of discharge from hospital assessed up to 18 months)
- Glucose and triglycerides measured in mmol/L(From date of admission to date of discharge from hospital assessed up to 18 months)
- INR as a ratio (Patient PT/Control PT)(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 +++(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(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)(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(From date of admission to date of discharge from hospital assessed up to 18 months)
- Vaccination status(At admission to hospital)
- Positive or negative NPA or throat swab result for respiratory panel as assessed by PCR(From date of admission to date of discharge from hospital assessed up to 18 months)