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Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)

Completed
Conditions
Hemophagocytic Lymphohistiocytosis
Registration Number
NCT03510650
Lead Sponsor
Charite University, Berlin, Germany
Brief Summary

Hemophagocytic lymphohistiocytosis in adults (HLH) is at 68% mortality whereas 78% of all cases remain undiagnosed though therapies are available which clearly reduce mortality. The investigators aim to systematically investigate this life-threatening hyperinflammatory syndrome in intensive care units (ICU) in order to detect biomarkers that are highly sensitive and highly specific for HLH in ICU compared to patients with sepsis.

Detailed Description

The investigators will draw blood samples of 100 patients at the time of diagnosis (each 50 with suspected or diagnosed HLH/sepsis) to determine a cytokine panel (c reactive protein (CRP), procalcitonin (PCT), interleukin (IL) 1β, IL-6, IL-8, IL-10, IL-18, IL-33, tumor necrosis factor (TNF) α, interferon (IFN) ɣ, soluble IL-2 receptor (sIL-2R), the EBV and CMV viral loads, human immunodeficiency virus (HIV) antibodies and -antigen, perforin, fibrinogen, triglycerides, bilirubin, lactate dehydrogenase, liver transaminases, sodium, serum albumin, electrophoresis, glycosylated ferritin, the microRNAs miR-205-5p, miR-194-5p and miR-30c-5p, perforin, CD107a and high immune status (differential blood count, T cells, B cells, NK cells, T helper cells, cytotoxic T cells, CD4 / CD8 ratio, HLA-DR of CD8 +, CD11a of CD8, CD57 of CD8, CD28 of CD8 +, HLA-DR of monocytes, CD56bright and CD69 of NK cells). The results of this study serve the development of new clinical concepts in order to safely diagnose HLH at an early stage, to distinguish from sepsis and to reduce the fatal consequences.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria
  • Male or female critically ill patients
  • At least 18 years old
  • Suspected or diagnosed HLH
Exclusion Criteria
  • Female patients: Pregnancy
  • Female patients: Breastfeeding

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Incidence of HLH in intensive care units based on HLH-2004 criteriaUp to 180 days

HLH patients are followed up until the end of hospital stay or death.

Secondary Outcome Measures
NameTimeMethod
Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loadsUp to 180 days

1 blood sample collection at time of diagnosed HLH

Perforin and CD107aUp to 180 days

1 blood sample collection at time of diagnosed HLH

Human immunodeficiency virus antibodies and -antigenUp to 180 days

1 blood sample collection at time of diagnosed HLH

Liver transaminase (ASAT)Up to 180 days

ASAT \[U/l\]

SodiumUp to 180 days
Detailed immune statusUp to 180 days

The immune status is analyzed by differential blood count \[/nl\], T cells \[/nl\], B cells \[/nl\], NK cells \[/nl\], T helper cells \[/nl\], cytotoxic T cells \[/nl\], CD4 / CD8 ratio, HLA-DR of CD8+ \[%\], CD11a of CD8 \[%\], CD57 of CD8 \[%\], CD28 of CD8+ \[%\], HLA-DR of monocytes \[antigen/cell\], CD56bright \[%\] and CD69 \[%\] of NK cells.

MortalityUp to 180 days

Mortality after 30 and 180 days

BilirubinUp to 180 days
Serum albuminUp to 180 days
Cytokine panelUp to 180 days

1 blood sample of Cytokine panel (CRP, PCT, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33, TNF-α, IFN-ɣ, sIL-2R, ferritin) collection at time of diagnosed HLH

FibrinogenUp to 180 days
Liver transaminases (ALAT)Up to 180 days

ALAT \[U/l\]

Glycosylated ferritinUp to 180 days

1 blood sample collection at time of diagnosed HLH

Intensive care unit stayParticipants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks
Hospital stayParticipants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks
Lactate dehydrogenaseUp to 180 days

Lactate dehydrogenase is measured in U/l

microRNAs miR-205-5p, miR-194-5p and miR-30c-5pUp to 180 days

1 blood sample collection at time of diagnosed HLH

TriglyceridesUp to 180 days
Serum protein electrophoresisUp to 180 days

Serum protein Electrophoresis (%) is used to separate and quantify the serum protein components into serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma Globulins.

Trial Locations

Locations (1)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin

🇩🇪

Berlin, Germany

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