primary EBV infection in children
Conditions
Interventions
Glucocorticoid Therapy Group(Part 3Randomized Controlled Trial of Early Glucocorticoid Immune Intervention for EBV-Associated Sepsis or Suspected EBV-HLH in Children):Glucocorticoid therapy along with
Control Group(Part 3Randomized Controlled Trial of Early Glucocorticoid Immune Intervention for EBV-Associated Sepsis or Suspected EBV-HLH in Children):antiviral, fluid supplementation, hepatoprotecti
Antiviral Therapy Group(Part 3Assessment of the Effectiveness of Antiviral Drug Treatment for Pediatric EBV Heterologous Infections):antiviral, fluid supplementation, hepatoprotective, and other sympt
Control Group(Part 3Assessment of the Effectiveness of Antiviral Drug Treatment for Pediatric EBV Heterologous Infections):fluid supplementation, hepatoprotective, and other symptomatic treatments
Observation Group:NA
Sponsors
The Children's Hospital, Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
1 Years to 18 Years
Inclusion criteria
Inclusion criteria: Part I: (1) Meet any 1 or more of the following IM clinical manifestations: ? Fever; ? Pharyngeal inflammation; ? Enlarged cervical lymph nodes; ? Hepatomegaly; ? Splenomegaly; ? Periorbital edema (2) Meet the positive criteria for serum or plasma EBV-DNA. Part II: Same inclusion criteria as Part I. Part III: Assessment of the Effectiveness of Antiviral Drug Treatment for Pediatric EBV Heterologous Infections: Eligible according to the inclusion criteria of Part I, and simultaneously classified as low-risk and high-risk based on the study results of Part I. Part III: Randomized Controlled Trial of Early Glucocorticoid Immune Intervention for EBV-Associated Sepsis or Suspected EBV-HLH in Children: Inclusion Criteria (meeting all conditions of 1, 6-9, and at least one of 2-5) (1) Age =6 months and 38°C) for =7 days. (3) Patients have a fever within 24 hours of enrollment and a white blood cell count =15×10^9/L within 48 hours before and after enrollment, and alanine aminotransferase greater than twice the upper limit of normal for each center within 48 hours before and after enrollment. (4) Meet the diagnostic criteria for sepsis, see Study Methods 1.3.1 for details. (5) Meet at least three of the HLH-2004 criteria, but not yet 5. (6) Laboratory evidence of EBV infection (meeting any one of the five): ?For individuals over 6 years old, L% >50% or L > 5×10^9/L; ?Atypical lymphocytes >10%; ?Positive VCA-IgM and VCA-IgG, and negative NA-IgG; ?Negative VCA-IgM and positive low-affinity VCA-IgG; ?Positive serum EBV-DNA. (7) The interval between the first appearance of EBV infection-related symptoms (fever, pharyngitis, eyelid edema, lymph node enlargement) and randomization is =14 days. (8) Able to comply with all study procedures and able to complete the subject questionnaire as required by the trial (the subject's guardian may assist in completing if necessary). (9) The subject and their guardian are willing to voluntarily participate in the study and have signed the informed consent form.
Exclusion criteria
Exclusion criteria: Part I: (1) A confirmed diagnosis of CAEBV (Chronic Active Epstein-Barr Virus infection); (2) A confirmed diagnosis of EBV-HLH (Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis); (3) Treatment with glucocorticoids and intravenous immunoglobulin has been administered. Part II: Meets the exclusion criteria of Part I. Part III: Assessment of the Effectiveness of Antiviral Drug Treatment for Pediatric EBV Heterologous Infections: Meets the exclusion criteria of Part I and has been confirmed to have EBV infection with the use of antiviral drugs other than ganciclovir after the diagnosis. Part III: Randomized Controlled Trial of Early Glucocorticoid Immune Intervention for EBV-Associated Sepsis or Suspected EBV-HLH in Children: (1) History of previous EBV infection or chronic EBV infection. (2) Clear concurrent acute or chronic infection with other pathogens. (3) Concurrent severe complications of EBV infection (for detailed definitions, see study endpoints): Hemophagocytic syndrome, splenic rupture, acute liver failure, neurological complications (including encephalitis, aseptic meningitis, epilepsy, Guillain-Barré syndrome, and other peripheral neuropathies, multiple sclerosis, and acute disseminated encephalomyelitis, etc., central nervous system inflammatory demyelinating diseases), hematological complications (including neutropenia, severe thrombocytopenia, and severe hemolytic anemia), respiratory complications (pneumonia, grade III-IV laryngeal obstruction). (4) Concurrent other diseases affecting liver function: Hepatitis, fatty liver, drug-induced liver injury, alcoholic liver disease, autoimmune liver disease, genetic metabolic liver disease, liver cancer, bile duct cancer, bile duct infection, bile duct parasitic diseases, etc. (5) Concurrent other severe underlying diseases and critical illnesses: Deformations that severely affect organ function, severe malnutrition, immune deficiency or chromosomal abnormalities, genetic metabolic diseases, post stem cell transplantation, post solid organ transplantation, malignant tumors, autoimmune diseases, epilepsy, severe mental history, respiratory failure, heart failure, shock, multiple organ dysfunction, etc. (6) Received glucocorticoids or other immunosuppressants or immunoglobulins or drugs affecting liver function within 14 days. (7) Known contraindications to study-related drugs (ganciclovir, methylprednisolone) (including but not limited to): Allergy to study drugs, active peptic ulcer, recent gastrointestinal anastomosis, fracture or other trauma repair period, severe osteoporosis, herpes simplex keratoconjunctivitis and ulcerative keratitis/cornal ulcer, severe hypertension, severe diabetes, fungal infections, chickenpox, cataracts or glaucoma. (8) Participated in another clinical trial within 30 days and used any other clinical trial medication or devices. (9) Deemed unsuitable to participate in this clinical study by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Viral load changes within T, NK lymphocytes(Part 4);The proportion of patients who progress to meet 5 out of 8 HLH-2004 criteria(Part 4);Part 1: Rate of progression to Sepsis;Part 3: ICU Stay Duration.;Part 3: Changes in EBV Viral Load in Ectopic Infected Cells.;Part 3: Hospital Stay Duration;Part 3: Maximum Drug Concentration and Time;Part 1: Rate of progression to EBV-HLH;Part 1: Rate of progression to CAEBV;Part 1: Rate of progression to Neoplastic Diseases;Part 3: Number of Fever Days;Part 3:Hospital Stay Duration;Part 3: ICU Admission Rate;Part 3: Hospitalization Costs;Part 3: Drug Half-Life; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of fever(Part 4);Liver dysfunction(Part 4);Other organs dysfunction(Part 4);Duration of Viral Positivity(Part 4);Length of hospital stay(Part 4);Length of ICU stay(Part 4);Changes in ferritin and cytokine levels of IL-6, IL-10, and IFN-? between baseline and day 4(Part 4);All-cause mortality at day 90 post-randomization(Part 4);Part 3: Area Under the Pharmacokinetic Curve from 0 to 72 Hours; | — |
Countries
China
Contacts
Public ContactLisu Huang
The Children's Hospital, Zhejiang University School of Medicine
Outcome results
None listed